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1. A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children

Author

Isobel S. Walker, Saber Dini, Elizabeth H. Aitken, Timon Damelang, Wina Hasang, Agersew Alemu, Anja T. R. Jensen, Janavi S. Rambhatla, D. Herbert Opi, Michael F. Duffy, Eizo Takashima, Visopo Harawa, Takafumi Tsuboi, Julie A. Simpson, Wilson Mandala, Terrie E. Taylor, Karl B. Seydel, Amy W. Chung, and Stephen J. Rogerson

Subjects
Plasmodium falciparum, Malawi, Antibody, Immunity, Africa, Medicine
Abstract

Abstract Background Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins are expressed on the surface of infected erythrocytes, mediating parasite sequestration in the vasculature. PfEMP1 is a major target of protective antibodies, but the features of the antibody response are poorly defined. Methods In Malawian children with cerebral or uncomplicated malaria, we characterized the antibody response to 39 recombinant PfEMP1 Duffy binding like (DBL) domains or cysteine-rich interdomain regions (CIDRs) in detail, including measures of antibody classes, subclasses, and engagement with Fcγ receptors and complement. Using elastic net regularized logistic regression, we identified a combination of seven antibody targets and Fc features that best distinguished between children with cerebral and uncomplicated malaria. To confirm the role of the selected targets and Fc features, we measured antibody-dependent neutrophil and THP-1 cell phagocytosis of intercellular adhesion molecule-1 (ICAM-1) and endothelial protein C (EPCR) co-binding infected erythrocytes. Results The selected features distinguished between children with cerebral and uncomplicated malaria with 87% accuracy (median, 80–96% interquartile range) and included antibody to well-characterized DBLβ3 domains and a less well-characterized CIDRγ12 domain. The abilities of antibodies to engage C1q and FcγRIIIb, rather than levels of IgG, correlated with protection. In line with a role of FcγRIIIb binding antibodies to DBLβ3 domains, antibody-dependent neutrophil phagocytosis of ICAM-1 and EPCR co-binding IE was higher in uncomplicated malaria (15% median, 8–38% interquartile range) compared to cerebral malaria (7%, 30–15%, p

Published
2024
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2. Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children

Author

Janice Z. Jia, Carolyn A. Cohen, Haogao Gu, Milla R. McLean, Raghavan Varadarajan, Nisha Bhandari, Malik Peiris, Gabriel M. Leung, Leo L. M. Poon, Tim Tsang, Amy W. Chung, Benjamin J. Cowling, Nancy H. L. Leung, and Sophie A. Valkenburg

Subjects
Science
Abstract

Abstract Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered ‘elite influenza controllers’.

Published
2024
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3. An acute rheumatic fever immune signature comprising inflammatory markers, IgG3, and Streptococcus pyogenes-specific antibodies

Author

Natalie Lorenz, Reuben McGregor, Alana L. Whitcombe, Prachi Sharma, Ciara Ramiah, Francis Middleton, Michael G. Baker, William J. Martin, Nigel J. Wilson, Amy W. Chung, and Nicole J. Moreland

Subjects
Immunology, Immune response, Microbiology, Cell biology, Science
Abstract

Summary: Understanding the immune profile of acute rheumatic fever (ARF), a serious post-infectious sequelae of Streptococcal pyogenes (group A Streptococcus [GAS]), could inform disease pathogenesis and management. Circulating cytokines, immunoglobulins, and complement were analyzed in participants with first-episode ARF, swab-positive GAS pharyngitis and matched healthy controls. A striking elevation of total IgG3 was observed in ARF (90% > clinical reference range for normal). ARF was also associated with an inflammatory triad with significant correlations between interleukin-6, C-reactive protein, and complement C4 absent in controls. Quantification of GAS-specific antibody responses revealed that subclass polarization was remarkably consistent across the disease spectrum; conserved protein antigens polarized to IgG1, while M-protein responses polarized to IgG3 in all groups. However, the magnitude of responses was significantly higher in ARF. Taken together, these findings emphasize the association of exaggerated GAS antibody responses, IgG3, and inflammatory cytokines in ARF and suggest IgG3 testing could beneficially augment clinical diagnosis.

Published
2024
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5. The distinct translational landscapes of gram-negative Salmonella and gram-positive Listeria

Author

Owain J. Bryant, Filip Lastovka, Jessica Powell, and Betty Y. -W. Chung

Subjects
Science
Abstract

Abstract Translational control in pathogenic bacteria is fundamental to gene expression and affects virulence and other infection phenotypes. We used an enhanced ribosome profiling protocol coupled with parallel transcriptomics to capture accurately the global translatome of two evolutionarily distant pathogenic bacteria—the Gram-negative bacterium Salmonella and the Gram-positive bacterium Listeria. We find that the two bacteria use different mechanisms to translationally regulate protein synthesis. In Salmonella, in addition to the expected correlation between translational efficiency and cis-regulatory features such as Shine–Dalgarno (SD) strength and RNA secondary structure around the initiation codon, our data reveal an effect of the 2nd and 3rd codons, where the presence of tandem lysine codons (AAA-AAA) enhances translation in both Salmonella and E. coli. Strikingly, none of these features are seen in efficiently translated Listeria transcripts. Instead, approximately 20% of efficiently translated Listeria genes exhibit 70 S footprints seven nt upstream of the authentic start codon, suggesting that these genes may be subject to a novel translational initiation mechanism. Our results show that SD strength is not a direct hallmark of translational efficiency in all bacteria. Instead, Listeria has evolved additional mechanisms to control gene expression level that are distinct from those utilised by Salmonella and E. coli.

Published
2023
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7. Immunoglobulin G genetic variation can confound assessment of antibody levels via altered binding to detection reagents

Author

Ruth A Purcell, L Carissa Aurelia, Robyn Esterbauer, Lilith F Allen, Katherine A Bond, Deborah A Williamson, Janine M Trevillyan, Jason A Trubiano, Jennifer J Juno, Adam K Wheatley, Miles P Davenport, Thi HO Nguyen, Katherine Kedzierska, Stephen J Kent, Kevin John Selva, and Amy W Chung

Subjects
allotype, anti‐immunoglobulin, IgG, polymorphisms, reproducibility, serology, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti‐Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel of commercial monoclonal anti‐IgG1 clones for capacity to universally recognise two dominant IgG1 haplotypes (G1m‐1,3 and G1m1,17). Methods Four commercial monoclonal anti‐human IgG1 clones were assessed via ELISAs and multiplex bead‐based assays for their ability to bind G1m‐1,3 and G1m1,17 IgG1 variants. Detection antibodies were validated against monoclonal IgG1 allotype standards and tested for capacity to recognise antigen‐specific plasma IgG1 from G1m‐1,3 and G1m1,17 homozygous and heterozygous SARS‐CoV‐2 BNT162b2 vaccinated (n = 28) and COVID‐19 convalescent (n = 44) individuals. An Fc‐specific pan‐IgG detection antibody corroborated differences between hinge‐ and Fc‐specific anti‐IgG1 responses. Results Hinge‐specific anti‐IgG1 clone 4E3 preferentially bound G1m1,17 compared to G1m‐1,3 IgG1. Consequently, SARS‐CoV‐2 Spike‐specific IgG1 levels detected in G1m1,17/G1m1,17 BNT162b2 vaccinees appeared 9‐ to 17‐fold higher than in G1m‐1,3/G1m‐1,3 vaccinees. Fc‐specific IgG1 and pan‐IgG detection antibodies equivalently bound G1m‐1,3 and G1m1,17 IgG1 variants, and detected comparable Spike‐specific IgG1 levels between haplotypes. IgG1 responses against other human coronaviruses and influenza were similarly poorly detected by 4E3 anti‐IgG1 in G1m‐1,3/G1m‐1,3 subjects. Conclusion Anti‐IgG1 clone 4E3 confounds assessment of antibody responses in clinical cohorts owing to bias towards detection of G1m1,17 IgG1 variants. Validation of anti‐Ig clones should include evaluation of binding to relevant antibody variants, particularly as the role of immunogenetics upon humoral immunity is increasingly explored in diverse populations.

Published
2024
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8. Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose boosterResearch in context

Author

Terry M. Nolan, Georgia Deliyannis, Maryanne Griffith, Sabine Braat, Lilith F. Allen, Jennifer Audsley, Amy W. Chung, Marcin Ciula, Nicholas A. Gherardin, Michelle L. Giles, Tom P. Gordon, Samantha L. Grimley, Lana Horng, David C. Jackson, Jennifer A. Juno, Katherine Kedzierska, Stephen J. Kent, Sharon R. Lewin, Mason Littlejohn, Hayley A. McQuilten, Francesca L. Mordant, Thi H.O. Nguyen, Vanessa Pac Soo, Briony Price, Damian F.J. Purcell, Pradhipa Ramanathan, Samuel J. Redmond, Steven Rockman, Zheng Ruan, Joseph Sasadeusz, Julie A. Simpson, Kanta Subbarao, Stewart A. Fabb, Thomas J. Payne, Asuka Takanashi, Chee Wah Tan, Joseph Torresi, Jing Jing Wang, Lin-Fa Wang, Hareth Al-Wassiti, Chinn Yi Wong, Sophie Zaloumis, Colin W. Pouton, and Dale I. Godfrey

Subjects
SARS-CoV-2, Vaccine, Receptor binding domain, Recombinant protein, mRNA, Beta variant, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting SARS-CoV-2 beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG1 Fc-fusion protein, and an mRNA encoding a membrane-anchored RBD. Methods: 76 healthy adults aged 18–64 y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59®, CSL Seqirus) protein vaccine (5, 15 or 45 μg, N = 32), mRNA vaccine (10, 20, or 50 μg, N = 32), or placebo (saline, N = 12) at least 90 days after a 3rd boost vaccination or SARS-CoV-2 infection. Bleeds occurred on days 1 (prior to vaccination), 8, and 29. ClinicalTrials.gov NCT05272605. Findings: No vaccine-related serious or medically-attended adverse events occurred. The protein vaccine reactogenicity was mild, whereas the mRNA vaccine was moderately reactogenic at higher dose levels. Best anti-RBD antibody responses resulted from the higher doses of each vaccine. A similar pattern was seen with live virus neutralisation and surrogate, and pseudovirus neutralisation assays. Breadth of immune response was demonstrated against BA.5 and more recent omicron subvariants (XBB, XBB.1.5 and BQ.1.1). Binding antibody titres for both vaccines were comparable to those of a licensed bivalent mRNA vaccine. Both vaccines enhanced CD4+ and CD8+ T cell activation. Interpretation: There were no safety concerns and the reactogenicity profile was mild and similar to licensed SARS-CoV-2 vaccines. Both vaccines showed strong immune boosting against beta, ancestral and omicron strains. Funding: Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.

Published
2023
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9. Reference compounds for characterizing cellular injury in high-content cellular morphology assays

Author

Jayme L. Dahlin, Bruce K. Hua, Beth E. Zucconi, Shawn D. Nelson, Shantanu Singh, Anne E. Carpenter, Jonathan H. Shrimp, Evelyne Lima-Fernandes, Mathias J. Wawer, Lawrence P. W. Chung, Ayushi Agrawal, Mary O’Reilly, Dalia Barsyte-Lovejoy, Magdalena Szewczyk, Fengling Li, Parnian Lak, Matthew Cuellar, Philip A. Cole, Jordan L. Meier, Tim Thomas, Jonathan B. Baell, Peter J. Brown, Michael A. Walters, Paul A. Clemons, Stuart L. Schreiber, and Bridget K. Wagner

Subjects
Science
Abstract

Cellular nuisance compounds are a burden in chemical biology and drug screening. Here the authors profile prototypical cytotoxic and nuisance compounds using the cell painting assay to systematically characterise cellular morphologies associated with compound-dependent cellular injury and nuisance activity.

Published
2023
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10. Effects of Temperature and Salinity on Perfluorooctane Sulfonate (PFOS) Toxicity in Larval Estuarine Organisms

Author

Katy W. Chung, Peter B. Key, Philip Tanabe, and Marie E. DeLorenzo

Subjects
PFOS, fish, crustaceans, gastropods, toxicity, salinity, Chemical technology, TP1-1185
Abstract

Perfluorooctane sulfonate (PFOS) is a persistent contaminant that has been found globally within the environment. Key data gaps exist in the toxicity of PFOS to marine organisms, especially estuarine species that are crucial to the food web: fish, shrimp, and mollusks. This study developed toxicity thresholds for larval estuarine species, including grass shrimp (Palaemon pugio), sheepshead minnows (Cyprinodon variegatus), mysids (Americamysis bahia), and Eastern mud snails (Tritia obsoleta). Multiple abiotic stressors (salinity and temperature) were included as variables in testing the toxicity of PFOS. Acute 96 h toxicity testing under standard test conditions of 25 °C and 20 ppt seawater yielded LC50 values of 0.919 mg/L for C. variegatus, 1.375 mg/L for A. bahia, 1.559 mg/L for T. obsoleta, and 2.011 mg/L for P. pugio. The effects of increased temperature (32 °C) and decreased salinity (10 ppt) varied with test species. PFOS toxicity for the sheepshead minnows increased with temperature but was not altered by decreased salinity. For grass shrimp and mud snails, PFOS toxicity was greater under lower salinity. The combination of higher temperature and lower salinity was observed to lower the toxicity thresholds for all species. These data demonstrate that expanding toxicity testing to include a wider range of parameters will improve the environmental risk assessment of chemical contaminants, especially for species inhabiting dynamic estuarine ecosystems.

Published
2024
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11. Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections

Author

Kevin J. Selva, Pradhipa Ramanathan, Ebene R. Haycroft, Arnold Reynaldi, Deborah Cromer, Chee Wah Tan, Lin-Fa Wang, Bruce D. Wines, P. Mark Hogarth, Laura E. Downie, Samantha K. Davis, Ruth A. Purcell, Helen E. Kent, Jennifer A. Juno, Adam K. Wheatley, Miles P. Davenport, Stephen J. Kent, and Amy W. Chung

Subjects
COVID-19, Medicine
Abstract

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19–recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19–recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19–uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2–specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2–specific antibody responses and has implications for long-term protection from COVID-19.

Published
2023
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12. Acute diplopia after glabellar hyaluronic acid filler injection

Author

Caroline W. Chung, Eric J. Shiuey, César A. Briceño, and Vivian Lee

Subjects
Facial filler injection, Diplopia, Hyaluronic acid, Skin necrosis, Scarring, Ophthalmology, RE1-994
Abstract

Purpose: Blindness is a well-known complication of filler injection in the glabellar region. Acute diplopia from filler injection without vision loss is a rare complication that typically results in clinical ophthalmoplegia which can have permanent sequelae. Here, we describe a patient who presented with acute diplopia with grossly intact full extraocular motility after glabella hyaluronic acid filler injection that resolved after 1 month. Observations: A previously healthy 43-year-old woman underwent her first hyaluronic acid injection in the glabella and developed immediate binocular double vision with severe pain and skin mottling above her right eyebrow and central forehead. Hyaluronidase injections, nitroglycerin paste, and aspirin were immediately administered. On exam, there was significant skin mottling over the glabella, extending to the forehead and nose with a small incomitant horizontal and vertical misalignment. No changes to her vision were observed and extraocular motility was grossly full. The rest of her exam was unremarkable. Over the course of the following month, the patient's diplopia resolved, but she developed skin necrosis and scarring. Conclusions: Importance: Proper knowledge of facial and periocular anatomy is critical for practitioners to safely perform filler injections and manage potential complications. Patients should be counseled about the potential rare risks of these elective procedures.

Published
2023
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13. Acquisition of antibodies to Plasmodium falciparum and Plasmodium vivax antigens in pregnant women living in a low malaria transmission area of Brazil

Author

Meseret W. Kassa, Wina Hasang, André Barateiro, Timon Damelang, Jessica Brewster, Jamille G. Dombrowski, Rhea J. Longley, Amy W. Chung, Gerhard Wunderlich, Ivo Mueller, Elizabeth H. Aitken, Claudio R. F. Marinho, and Stephen J. Rogerson

Subjects
Pregnancy malaria, Antibody, P. falciparum, P. vivax, Low transmission, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Pregnant women have increased susceptibility to Plasmodium falciparum malaria and acquire protective antibodies over successive pregnancies. Most studies that investigated malaria antibody responses in pregnant women are from high transmission areas in sub-Saharan Africa, while reports from Latin America are scarce and inconsistent. The present study sought to explore the development of antibodies against P. falciparum and Plasmodium vivax antigens in pregnant women living in a low transmission area in the Brazilian Amazon. Methods In a prospective cohort study, plasma samples from 408 pregnant women (of whom 111 were infected with P. falciparum, 96 had infections with P. falciparum and P. vivax, and 201 had no Plasmodium infection) were used to measure antibody levels. Levels of IgG and opsonizing antibody to pregnancy-specific variant surface antigens (VSAs) on infected erythrocytes (IEs), 10 recombinant VAR2CSA Duffy binding like (DBL domains), 10 non-pregnancy-specific P. falciparum merozoite antigens, and 10 P. vivax antigens were measured by flow cytometry, ELISA, and multiplex assays. Antibody levels and seropositivity among the groups were compared. Results Antibodies to VSAs on P. falciparum IEs were generally low but were higher in currently infected women and women with multiple P. falciparum episodes over pregnancy. Many women (21%-69%) had antibodies against each individual VAR2CSA DBL domain, and antibodies to DBLs correlated with each other (r ≥ 0.55, p

Published
2022
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14. Releasing chemical energy in spatially programmed ferroelectrics

Author

Yong Hu, Jennifer L. Gottfried, Rose Pesce-Rodriguez, Chi-Chin Wu, Scott D. Walck, Zhiyu Liu, Sangeeth Balakrishnan, Scott Broderick, Zipeng Guo, Qiang Zhang, Lu An, Revant Adlakha, Mostafa Nouh, Chi Zhou, Peter W. Chung, and Shenqiang Ren

Subjects
Science
Abstract

Chemical energy ferroelectrics show limited control of the energy release rate. Here, the authors design spatially programmed energetic ferroelectrics with controlled energy release rates from machine learning-directed additive manufacturing and ice-templating assembly.

Published
2022
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15. Search for Dark Matter Axions with CAST-CAPP

Author

C. M. Adair, K. Altenmüller, V. Anastassopoulos, S. Arguedas Cuendis, J. Baier, K. Barth, A. Belov, D. Bozicevic, H. Bräuninger, G. Cantatore, F. Caspers, J. F. Castel, S. A. Çetin, W. Chung, H. Choi, J. Choi, T. Dafni, M. Davenport, A. Dermenev, K. Desch, B. Döbrich, H. Fischer, W. Funk, J. Galan, A. Gardikiotis, S. Gninenko, J. Golm, M. D. Hasinoff, D. H. H. Hoffmann, D. Díez Ibáñez, I. G. Irastorza, K. Jakovčić, J. Kaminski, M. Karuza, C. Krieger, Ç. Kutlu, B. Lakić, J. M. Laurent, J. Lee, S. Lee, G. Luzón, C. Malbrunot, C. Margalejo, M. Maroudas, L. Miceli, H. Mirallas, L. Obis, A. Özbey, K. Özbozduman, M. J. Pivovaroff, M. Rosu, J. Ruz, E. Ruiz-Chóliz, S. Schmidt, M. Schumann, Y. K. Semertzidis, S. K. Solanki, L. Stewart, I. Tsagris, T. Vafeiadis, J. K. Vogel, M. Vretenar, S. Youn, and K. Zioutas

Subjects
Science
Abstract

Haloscopes aim at detecting axions by converting them into photons using high-quality resonant cavities, where the cavity resonance should be tuned with the unknown axion mass. Here, the authors improve exclusion limits using four phase-matched resonant cavities and a fast frequency scanning technique.

Published
2022
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18. Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

Author

Ruth A. Purcell, Robert M. Theisen, Kelly B. Arnold, Amy W. Chung, and Kevin J. Selva

Subjects
antibody, allotype, polymorphism, Fc receptor, Fc function, computational modelling, Immunologic diseases. Allergy, RC581-607
Abstract

Vaccine efficacy determined within the controlled environment of a clinical trial is usually substantially greater than real-world vaccine effectiveness. Typically, this results from reduced protection of immunologically vulnerable populations, such as children, elderly individuals and people with chronic comorbidities. Consequently, these high-risk groups are frequently recommended tailored immunisation schedules to boost responses. In addition, diverse groups of healthy adults may also be variably protected by the same vaccine regimen. Current population-based vaccination strategies that consider basic clinical parameters offer a glimpse into what may be achievable if more nuanced aspects of the immune response are considered in vaccine design. To date, vaccine development has been largely empirical. However, next-generation approaches require more rational strategies. We foresee a generation of precision vaccines that consider the mechanistic basis of vaccine response variations associated with both immunogenetic and baseline health differences. Recent efforts have highlighted the importance of balanced and diverse extra-neutralising antibody functions for vaccine-induced protection. However, in immunologically vulnerable populations, significant modulation of polyfunctional antibody responses that mediate both neutralisation and effector functions has been observed. Here, we review the current understanding of key genetic and inflammatory modulators of antibody polyfunctionality that affect vaccination outcomes and consider how this knowledge may be harnessed to tailor vaccine design for improved public health.

Published
2023
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19. Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccineResearch in context

Author

Georgia Deliyannis, Nicholas A. Gherardin, Chinn Yi Wong, Samantha L. Grimley, James P. Cooney, Samuel J. Redmond, Paula Ellenberg, Kathryn C. Davidson, Francesca L. Mordant, Tim Smith, Marianne Gillard, Ester Lopez, Julie McAuley, Chee Wah Tan, Jing J. Wang, Weiguang Zeng, Mason Littlejohn, Runhong Zhou, Jasper Fuk-Woo Chan, Zhi-wei Chen, Airn E. Hartwig, Richard Bowen, Jason M. Mackenzie, Elizabeth Vincan, Joseph Torresi, Katherine Kedzierska, Colin W. Pouton, Tom P. Gordon, Lin-fa Wang, Stephen J. Kent, Adam K. Wheatley, Sharon R. Lewin, Kanta Subbarao, Amy W. Chung, Marc Pellegrini, Trent Munro, Terry Nolan, Steven Rockman, David C. Jackson, Damian F.J. Purcell, and Dale I. Godfrey

Subjects
SARS-CoV-2, COVID-19, Vaccine, Receptor-binding domain, RBD, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. Findings: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The ‘beta variant’ RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. Interpretation: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. Funding: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.

Published
2023
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20. Mixture Effects of Per- and Polyfluoroalkyl Substances on Embryonic and Larval Sheepshead Minnows (Cyprinodon variegatus)

Author

Philip Tanabe, Peter B. Key, Katy W. Chung, Emily C. Pisarski, Jessica L. Reiner, Alix E. Rodowa, Jason T. Magnuson, and Marie E. DeLorenzo

Subjects
PFAS, PFOS, PFOA, mixtures, mechanism of toxicity, PPARα, Chemical technology, TP1-1185
Abstract

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants originating from many everyday products. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are two PFAS that are commonly found at high concentrations in aquatic environments. Both chemicals have previously been shown to be toxic to fish, as well as having complex and largely uncharacterized mixture effects. However, limited information is available on marine and estuarine species. In this study, embryonic and larval sheepshead minnows (Cyprinodon variegatus) were exposed to several PFAS mixtures to assess lethal and sublethal effects. PFOS alone was acutely toxic to larvae, with a 96 h LC50 of 1.97 mg/L (1.64–2.16). PFOS + PFOA resulted in a larval LC50 of 3.10 (2.62–3.79) mg/L, suggesting an antagonistic effect. These observations were supported by significant reductions in malondialdehyde (105% ± 3.25) and increases in reduced glutathione concentrations (43.8% ± 1.78) in PFOS + PFOA exposures compared to PFOS-only treatments, indicating reduced oxidative stress. While PFOA reduced PFOS-induced mortality (97.0% ± 3.03), perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA) did not. PFOS alone did not affect expression of peroxisome proliferator-activated receptor alpha (pparα) but significantly upregulated apolipoprotein A4 (apoa4) (112.4% ± 17.8), a downstream product of pparα, while none of the other individually tested PFAS affected apoa4 expression. These findings suggest that there are antagonistic interactions between PFOA and PFOS that may reduce mixture toxicity in larval sheepshead minnows through reduced oxidative stress. Elucidating mechanisms of toxicity and interactions between PFAS will aid environmental regulation and management of these ubiquitous pollutants.

Published
2024
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21. GWTC-3: Compact Binary Coalescences Observed by LIGO and Virgo during the Second Part of the Third Observing Run

Author

R. Abbott, T. D. Abbott, F. Acernese, K. Ackley, C. Adams, N. Adhikari, R. X. Adhikari, V. B. Adya, C. Affeldt, D. Agarwal, M. Agathos, K. Agatsuma, N. Aggarwal, O. D. Aguiar, L. Aiello, A. Ain, P. Ajith, S. Akcay, T. Akutsu, S. Albanesi, A. Allocca, P. A. Altin, A. Amato, C. Anand, S. Anand, A. Ananyeva, S. B. Anderson, W. G. Anderson, M. Ando, T. Andrade, N. Andres, T. Andrić, S. V. Angelova, S. Ansoldi, J. M. Antelis, S. Antier, S. Appert, Koji Arai, Koya Arai, Y. Arai, S. Araki, A. Araya, M. C. Araya, J. S. Areeda, M. Arène, N. Aritomi, N. Arnaud, M. Arogeti, S. M. Aronson, K. G. Arun, H. Asada, Y. Asali, G. Ashton, Y. Aso, M. Assiduo, S. M. Aston, P. Astone, F. Aubin, C. Austin, S. Babak, F. Badaracco, M. K. M. Bader, C. Badger, S. Bae, Y. Bae, A. M. Baer, S. Bagnasco, Y. Bai, L. Baiotti, J. Baird, R. Bajpai, M. Ball, G. Ballardin, S. W. Ballmer, A. Balsamo, G. Baltus, S. Banagiri, D. Bankar, J. C. Barayoga, C. Barbieri, B. C. Barish, D. Barker, P. Barneo, F. Barone, B. Barr, L. Barsotti, M. Barsuglia, D. Barta, J. Bartlett, M. A. Barton, I. Bartos, R. Bassiri, A. Basti, M. Bawaj, J. C. Bayley, A. C. Baylor, M. Bazzan, B. Bécsy, V. M. Bedakihale, M. Bejger, I. Belahcene, V. Benedetto, D. Beniwal, T. F. Bennett, J. D. Bentley, M. BenYaala, F. Bergamin, B. K. Berger, S. Bernuzzi, C. P. L. Berry, D. Bersanetti, A. Bertolini, J. Betzwieser, D. Beveridge, R. Bhandare, U. Bhardwaj, D. Bhattacharjee, S. Bhaumik, I. A. Bilenko, G. Billingsley, S. Bini, R. Birney, O. Birnholtz, S. Biscans, M. Bischi, S. Biscoveanu, A. Bisht, B. Biswas, M. Bitossi, M.-A. Bizouard, J. K. Blackburn, C. D. Blair, D. G. Blair, R. M. Blair, F. Bobba, N. Bode, M. Boer, G. Bogaert, M. Boldrini, L. D. Bonavena, F. Bondu, E. Bonilla, R. Bonnand, P. Booker, B. A. Boom, R. Bork, V. Boschi, N. Bose, S. Bose, V. Bossilkov, V. Boudart, Y. Bouffanais, A. Bozzi, C. Bradaschia, P. R. Brady, A. Bramley, A. Branch, M. Branchesi, J. Brandt, J. E. Brau, M. Breschi, T. Briant, J. H. Briggs, A. Brillet, M. Brinkmann, P. Brockill, A. F. Brooks, J. Brooks, D. D. Brown, S. Brunett, G. Bruno, R. Bruntz, J. Bryant, T. Bulik, H. J. Bulten, A. Buonanno, R. Buscicchio, D. Buskulic, C. Buy, R. L. Byer, G. S. Cabourn Davies, L. Cadonati, G. Cagnoli, C. Cahillane, J. Calderón Bustillo, J. D. Callaghan, T. A. Callister, E. Calloni, J. Cameron, J. B. Camp, M. Canepa, S. Canevarolo, M. Cannavacciuolo, K. C. Cannon, H. Cao, Z. Cao, E. Capocasa, E. Capote, G. Carapella, F. Carbognani, J. B. Carlin, M. F. Carney, M. Carpinelli, G. Carrillo, G. Carullo, T. L. Carver, J. Casanueva Diaz, C. Casentini, G. Castaldi, S. Caudill, M. Cavaglià, F. Cavalier, R. Cavalieri, M. Ceasar, G. Cella, P. Cerdá-Durán, E. Cesarini, W. Chaibi, K. Chakravarti, S. Chalathadka Subrahmanya, E. Champion, C.-H. Chan, C. Chan, C. L. Chan, K. Chan, M. Chan, K. Chandra, P. Chanial, S. Chao, C. E. A. Chapman-Bird, P. Charlton, E. A. Chase, E. Chassande-Mottin, C. Chatterjee, Debarati Chatterjee, Deep Chatterjee, M. Chaturvedi, S. Chaty, K. Chatziioannou, C. Chen, H. Y. Chen, J. Chen, K. Chen, X. Chen, Y.-B. Chen, Y.-R. Chen, Z. Chen, H. Cheng, C. K. Cheong, H. Y. Cheung, H. Y. Chia, F. Chiadini, C-Y. Chiang, G. Chiarini, R. Chierici, A. Chincarini, M. L. Chiofalo, A. Chiummo, G. Cho, H. S. Cho, R. K. Choudhary, S. Choudhary, N. Christensen, H. Chu, Q. Chu, Y-K. Chu, S. Chua, K. W. Chung, G. Ciani, P. Ciecielag, M. Cieślar, M. Cifaldi, A. A. Ciobanu, R. Ciolfi, F. Cipriano, A. Cirone, F. Clara, E. N. Clark, J. A. Clark, L. Clarke, P. Clearwater, S. Clesse, F. Cleva, E. Coccia, E. Codazzo, P.-F. Cohadon, D. E. Cohen, L. Cohen, M. Colleoni, C. G. Collette, A. Colombo, M. Colpi, C. M. Compton, M. Constancio, Jr., L. Conti, S. J. Cooper, P. Corban, T. R. Corbitt, I. Cordero-Carrión, S. Corezzi, K. R. Corley, N. Cornish, D. Corre, A. Corsi, S. Cortese, C. A. Costa, R. Cotesta, M. W. Coughlin, J.-P. Coulon, S. T. Countryman, B. Cousins, P. Couvares, D. M. Coward, M. J. Cowart, D. C. Coyne, R. Coyne, J. D. E. Creighton, T. D. Creighton, A. W. Criswell, M. Croquette, S. G. Crowder, J. R. Cudell, T. J. Cullen, A. Cumming, R. Cummings, L. Cunningham, E. Cuoco, M. Curyło, P. Dabadie, T. Dal Canton, S. Dall’Osso, G. Dálya, A. Dana, L. M. DaneshgaranBajastani, B. D’Angelo, B. Danila, S. Danilishin, S. D’Antonio, K. Danzmann, C. Darsow-Fromm, A. Dasgupta, L. E. H. Datrier, V. Dattilo, I. Dave, M. Davier, D. Davis, M. C. Davis, E. J. Daw, P. F. de Alarcón, R. Dean, D. DeBra, M. Deenadayalan, J. Degallaix, M. De Laurentis, S. Deléglise, V. Del Favero, F. De Lillo, N. De Lillo, W. Del Pozzo, L. M. DeMarchi, F. De Matteis, V. D’Emilio, N. Demos, T. Dent, A. Depasse, R. De Pietri, R. De Rosa, C. De Rossi, R. DeSalvo, R. De Simone, S. Dhurandhar, M. C. Díaz, M. Diaz-Ortiz, Jr., N. A. Didio, T. Dietrich, L. Di Fiore, C. Di Fronzo, C. Di Giorgio, F. Di Giovanni, M. Di Giovanni, T. Di Girolamo, A. Di Lieto, B. Ding, S. Di Pace, I. Di Palma, F. Di Renzo, A. K. Divakarla, A. Dmitriev, Z. Doctor, L. D’Onofrio, F. Donovan, K. L. Dooley, S. Doravari, I. Dorrington, M. Drago, J. C. Driggers, Y. Drori, J.-G. Ducoin, P. Dupej, O. Durante, D. D’Urso, P.-A. Duverne, S. E. Dwyer, C. Eassa, P. J. Easter, M. Ebersold, T. Eckhardt, G. Eddolls, B. Edelman, T. B. Edo, O. Edy, A. Effler, S. Eguchi, J. Eichholz, S. S. Eikenberry, M. Eisenmann, R. A. Eisenstein, A. Ejlli, E. Engelby, Y. Enomoto, L. Errico, R. C. Essick, H. Estellés, D. Estevez, Z. Etienne, T. Etzel, M. Evans, T. M. Evans, B. E. Ewing, V. Fafone, H. Fair, S. Fairhurst, A. M. Farah, S. Farinon, B. Farr, W. M. Farr, N. W. Farrow, E. J. Fauchon-Jones, G. Favaro, M. Favata, M. Fays, M. Fazio, J. Feicht, M. M. Fejer, E. Fenyvesi, D. L. Ferguson, A. Fernandez-Galiana, I. Ferrante, T. A. Ferreira, F. Fidecaro, P. Figura, I. Fiori, M. Fishbach, R. P. Fisher, R. Fittipaldi, V. Fiumara, R. Flaminio, E. Floden, H. Fong, J. A. Font, B. Fornal, P. W. F. Forsyth, A. Franke, S. Frasca, F. Frasconi, C. Frederick, J. P. Freed, Z. Frei, A. Freise, R. Frey, P. Fritschel, V. V. Frolov, G. G. Fronzé, Y. Fujii, Y. Fujikawa, M. Fukunaga, M. Fukushima, P. Fulda, M. Fyffe, H. A. Gabbard, W. E. Gabella, B. U. Gadre, J. R. Gair, J. Gais, S. Galaudage, R. Gamba, D. Ganapathy, A. Ganguly, D. Gao, S. G. Gaonkar, B. Garaventa, F. García, C. García-Núñez, C. García-Quirós, F. Garufi, B. Gateley, S. Gaudio, V. Gayathri, G.-G. Ge, G. Gemme, A. Gennai, J. George, R. N. George, O. Gerberding, L. Gergely, P. Gewecke, S. Ghonge, Abhirup Ghosh, Archisman Ghosh, Shaon Ghosh, Shrobana Ghosh, B. Giacomazzo, L. Giacoppo, J. A. Giaime, K. D. Giardina, D. R. Gibson, C. Gier, M. Giesler, P. Giri, F. Gissi, J. Glanzer, A. E. Gleckl, P. Godwin, E. Goetz, R. Goetz, N. Gohlke, J. Golomb, B. Goncharov, G. González, A. Gopakumar, M. Gosselin, R. Gouaty, D. W. Gould, B. Grace, A. Grado, M. Granata, V. Granata, A. Grant, S. Gras, P. Grassia, C. Gray, R. Gray, G. Greco, A. C. Green, R. Green, A. M. Gretarsson, E. M. Gretarsson, D. Griffith, W. Griffiths, H. L. Griggs, G. Grignani, A. Grimaldi, S. J. Grimm, H. Grote, S. Grunewald, P. Gruning, D. Guerra, G. M. Guidi, A. R. Guimaraes, G. Guixé, H. K. Gulati, H.-K. Guo, Y. Guo, Anchal Gupta, Anuradha Gupta, P. Gupta, E. K. Gustafson, R. Gustafson, F. Guzman, S. Ha, L. Haegel, A. Hagiwara, S. Haino, O. Halim, E. D. Hall, E. Z. Hamilton, G. Hammond, W.-B. Han, M. Haney, J. Hanks, C. Hanna, M. D. Hannam, O. Hannuksela, H. Hansen, T. J. Hansen, J. Hanson, T. Harder, T. Hardwick, K. Haris, J. Harms, G. M. Harry, I. W. Harry, D. Hartwig, K. Hasegawa, B. Haskell, R. K. Hasskew, C.-J. Haster, K. Hattori, K. Haughian, H. Hayakawa, K. Hayama, F. J. Hayes, J. Healy, A. Heidmann, A. Heidt, M. C. Heintze, J. Heinze, J. Heinzel, H. Heitmann, F. Hellman, P. Hello, A. F. Helmling-Cornell, G. Hemming, M. Hendry, I. S. Heng, E. Hennes, J. Hennig, M. H. Hennig, A. G. Hernandez, F. Hernandez Vivanco, M. Heurs, S. Hild, P. Hill, Y. Himemoto, A. S. Hines, Y. Hiranuma, N. Hirata, E. Hirose, S. Hochheim, D. Hofman, J. N. Hohmann, D. G. Holcomb, N. A. Holland, K. Holley-Bockelmann, I. J. Hollows, Z. J. Holmes, K. Holt, D. E. Holz, Z. Hong, P. Hopkins, J. Hough, S. Hourihane, E. J. Howell, C. G. Hoy, D. Hoyland, A. Hreibi, B-H. Hsieh, Y. Hsu, G-Z. Huang, H-Y. Huang, P. Huang, Y-C. Huang, Y.-J. Huang, Y. Huang, M. T. Hübner, A. D. Huddart, B. Hughey, D. C. Y. Hui, V. Hui, S. Husa, S. H. Huttner, R. Huxford, T. Huynh-Dinh, S. Ide, B. Idzkowski, A. Iess, B. Ikenoue, S. Imam, K. Inayoshi, C. Ingram, Y. Inoue, K. Ioka, M. Isi, K. Isleif, K. Ito, Y. Itoh, B. R. Iyer, K. Izumi, V. JaberianHamedan, T. Jacqmin, S. J. Jadhav, S. P. Jadhav, A. L. James, A. Z. Jan, K. Jani, J. Janquart, K. Janssens, N. N. Janthalur, P. Jaranowski, D. Jariwala, R. Jaume, A. C. Jenkins, K. Jenner, C. Jeon, M. Jeunon, W. Jia, H.-B. Jin, G. R. Johns, N. K. Johnson-McDaniel, A. W. Jones, D. I. Jones, J. D. Jones, P. Jones, R. Jones, R. J. G. Jonker, L. Ju, P. Jung, K. Jung, J. Junker, V. Juste, K. Kaihotsu, T. Kajita, M. Kakizaki, C. V. Kalaghatgi, V. Kalogera, B. Kamai, M. Kamiizumi, N. Kanda, S. Kandhasamy, G. Kang, J. B. Kanner, Y. Kao, S. J. Kapadia, D. P. Kapasi, S. Karat, C. Karathanasis, S. Karki, R. Kashyap, M. Kasprzack, W. Kastaun, S. Katsanevas, E. Katsavounidis, W. Katzman, T. Kaur, K. Kawabe, K. Kawaguchi, N. Kawai, T. Kawasaki, F. Kéfélian, D. Keitel, J. S. Key, S. Khadka, F. Y. Khalili, S. Khan, E. A. Khazanov, N. Khetan, M. Khursheed, N. Kijbunchoo, C. Kim, J. C. Kim, J. Kim, K. Kim, W. S. Kim, Y.-M. Kim, C. Kimball, N. Kimura, M. Kinley-Hanlon, R. Kirchhoff, J. S. Kissel, N. Kita, H. Kitazawa, L. Kleybolte, S. Klimenko, A. M. Knee, T. D. Knowles, E. Knyazev, P. Koch, G. Koekoek, Y. Kojima, K. Kokeyama, S. Koley, P. Kolitsidou, M. Kolstein, K. Komori, V. Kondrashov, A. K. H. Kong, A. Kontos, N. Koper, M. Korobko, K. Kotake, M. Kovalam, D. B. Kozak, C. Kozakai, R. Kozu, V. Kringel, N. V. Krishnendu, A. Królak, G. Kuehn, F. Kuei, P. Kuijer, S. Kulkarni, A. Kumar, P. Kumar, Rahul Kumar, Rakesh Kumar, J. Kume, K. Kuns, C. Kuo, H-S. Kuo, Y. Kuromiya, S. Kuroyanagi, K. Kusayanagi, S. Kuwahara, K. Kwak, P. Lagabbe, D. Laghi, E. Lalande, T. L. Lam, A. Lamberts, M. Landry, B. B. Lane, R. N. Lang, J. Lange, B. Lantz, I. La Rosa, A. Lartaux-Vollard, P. D. Lasky, M. Laxen, A. Lazzarini, C. Lazzaro, P. Leaci, S. Leavey, Y. K. Lecoeuche, H. K. Lee, H. M. Lee, H. W. Lee, J. Lee, K. Lee, R. Lee, J. Lehmann, A. Lemaître, M. Leonardi, N. Leroy, N. Letendre, C. Levesque, Y. Levin, J. N. Leviton, K. Leyde, A. K. Y. Li, B. Li, J. Li, K. L. Li, T. G. F. Li, X. Li, C-Y. Lin, F-K. Lin, F-L. Lin, H. L. Lin, L. C.-C. Lin, F. Linde, S. D. Linker, J. N. Linley, T. B. Littenberg, G. C. Liu, J. Liu, K. Liu, X. Liu, F. Llamas, M. Llorens-Monteagudo, R. K. L. Lo, A. Lockwood, M. Loh, L. T. London, A. Longo, D. Lopez, M. Lopez Portilla, M. Lorenzini, V. Loriette, M. Lormand, G. Losurdo, T. P. Lott, J. D. Lough, C. O. Lousto, G. Lovelace, J. F. Lucaccioni, H. Lück, D. Lumaca, A. P. Lundgren, L.-W. Luo, J. E. Lynam, R. Macas, M. MacInnis, D. M. Macleod, I. A. O. MacMillan, A. Macquet, I. Magaña Hernandez, C. Magazzù, R. M. Magee, R. Maggiore, M. Magnozzi, S. Mahesh, E. Majorana, C. Makarem, I. Maksimovic, S. Maliakal, A. Malik, N. Man, V. Mandic, V. Mangano, J. L. Mango, G. L. Mansell, M. Manske, M. Mantovani, M. Mapelli, F. Marchesoni, M. Marchio, F. Marion, Z. Mark, S. Márka, Z. Márka, C. Markakis, A. S. Markosyan, A. Markowitz, E. Maros, A. Marquina, S. Marsat, F. Martelli, I. W. Martin, R. M. Martin, M. Martinez, V. A. Martinez, V. Martinez, K. Martinovic, D. V. Martynov, E. J. Marx, H. Masalehdan, K. Mason, E. Massera, A. Masserot, T. J. Massinger, M. Masso-Reid, S. Mastrogiovanni, A. Matas, M. Mateu-Lucena, F. Matichard, M. Matiushechkina, N. Mavalvala, J. J. McCann, R. McCarthy, D. E. McClelland, P. K. McClincy, S. McCormick, L. McCuller, G. I. McGhee, S. C. McGuire, C. McIsaac, J. McIver, T. McRae, S. T. McWilliams, D. Meacher, M. Mehmet, A. K. Mehta, Q. Meijer, A. Melatos, D. A. Melchor, G. Mendell, A. Menendez-Vazquez, C. S. Menoni, R. A. Mercer, L. Mereni, K. Merfeld, E. L. Merilh, J. D. Merritt, M. Merzougui, S. Meshkov, C. Messenger, C. Messick, P. M. Meyers, F. Meylahn, A. Mhaske, A. Miani, H. Miao, I. Michaloliakos, C. Michel, Y. Michimura, H. Middleton, L. Milano, A. L. Miller, A. Miller, B. Miller, M. Millhouse, J. C. Mills, E. Milotti, O. Minazzoli, Y. Minenkov, N. Mio, Ll. M. Mir, M. Miravet-Tenés, C. Mishra, T. Mishra, T. Mistry, S. Mitra, V. P. Mitrofanov, G. Mitselmakher, R. Mittleman, O. Miyakawa, A. Miyamoto, Y. Miyazaki, K. Miyo, S. Miyoki, Geoffrey Mo, L. M. Modafferi, E. Moguel, K. Mogushi, S. R. P. Mohapatra, S. R. Mohite, I. Molina, M. Molina-Ruiz, M. Mondin, M. Montani, C. J. Moore, D. Moraru, F. Morawski, A. More, C. Moreno, G. Moreno, Y. Mori, S. Morisaki, Y. Moriwaki, G. Morrás, B. Mours, C. M. Mow-Lowry, S. Mozzon, F. Muciaccia, Arunava Mukherjee, D. Mukherjee, Soma Mukherjee, Subroto Mukherjee, Suvodip Mukherjee, N. Mukund, A. Mullavey, J. Munch, E. A. Muñiz, P. G. Murray, R. Musenich, S. Muusse, S. L. Nadji, K. Nagano, S. Nagano, A. Nagar, K. Nakamura, H. Nakano, M. Nakano, R. Nakashima, Y. Nakayama, V. Napolano, I. Nardecchia, T. Narikawa, L. Naticchioni, B. Nayak, R. K. Nayak, R. Negishi, B. F. Neil, J. Neilson, G. Nelemans, T. J. N. Nelson, M. Nery, P. Neubauer, A. Neunzert, K. Y. Ng, S. W. S. Ng, C. Nguyen, P. Nguyen, T. Nguyen, L. Nguyen Quynh, W.-T. Ni, S. A. Nichols, A. Nishizawa, S. Nissanke, E. Nitoglia, F. Nocera, M. Norman, C. North, S. Nozaki, J. F. Nuño Siles, L. K. Nuttall, J. Oberling, B. D. O’Brien, Y. Obuchi, J. O’Dell, E. Oelker, W. Ogaki, G. Oganesyan, J. J. Oh, K. Oh, S. H. Oh, M. Ohashi, N. Ohishi, M. Ohkawa, F. Ohme, H. Ohta, M. A. Okada, Y. Okutani, K. Okutomi, C. Olivetto, K. Oohara, C. Ooi, R. Oram, B. O’Reilly, R. G. Ormiston, N. D. Ormsby, L. F. Ortega, R. O’Shaughnessy, E. O’Shea, S. Oshino, S. Ossokine, C. Osthelder, S. Otabe, D. J. Ottaway, H. Overmier, A. E. Pace, G. Pagano, M. A. Page, G. Pagliaroli, A. Pai, S. A. Pai, J. R. Palamos, O. Palashov, C. Palomba, H. Pan, K. Pan, P. K. Panda, H. Pang, P. T. H. Pang, C. Pankow, F. Pannarale, B. C. Pant, F. H. Panther, F. Paoletti, A. Paoli, A. Paolone, A. Parisi, H. Park, J. Park, W. Parker, D. Pascucci, A. Pasqualetti, R. Passaquieti, D. Passuello, M. Patel, M. Pathak, B. Patricelli, A. S. Patron, S. Paul, E. Payne, M. Pedraza, M. Pegoraro, A. Pele, F. E. Peña Arellano, S. Penn, A. Perego, A. Pereira, T. Pereira, C. J. Perez, C. Périgois, C. C. Perkins, A. Perreca, S. Perriès, J. Petermann, D. Petterson, H. P. Pfeiffer, K. A. Pham, K. S. Phukon, O. J. Piccinni, M. Pichot, M. Piendibene, F. Piergiovanni, L. Pierini, V. Pierro, G. Pillant, M. Pillas, F. Pilo, L. Pinard, I. M. Pinto, M. Pinto, B. Piotrzkowski, K. Piotrzkowski, M. Pirello, M. D. Pitkin, E. Placidi, L. Planas, W. Plastino, C. Pluchar, R. Poggiani, E. Polini, D. Y. T. Pong, S. Ponrathnam, P. Popolizio, E. K. Porter, R. Poulton, J. Powell, M. Pracchia, T. Pradier, A. K. Prajapati, K. Prasai, R. Prasanna, G. Pratten, M. Principe, G. A. Prodi, L. Prokhorov, P. Prosposito, L. Prudenzi, A. Puecher, M. Punturo, F. Puosi, P. Puppo, M. Pürrer, H. Qi, V. Quetschke, R. Quitzow-James, N. Qutob, F. J. Raab, G. Raaijmakers, H. Radkins, N. Radulesco, P. Raffai, S. X. Rail, S. Raja, C. Rajan, K. E. Ramirez, T. D. Ramirez, A. Ramos-Buades, J. Rana, P. Rapagnani, U. D. Rapol, A. Ray, V. Raymond, N. Raza, M. Razzano, J. Read, L. A. Rees, T. Regimbau, L. Rei, S. Reid, S. W. Reid, D. H. Reitze, P. Relton, A. Renzini, P. Rettegno, A. Reza, M. Rezac, F. Ricci, D. Richards, J. W. Richardson, L. Richardson, G. Riemenschneider, K. Riles, S. Rinaldi, K. Rink, M. Rizzo, N. A. Robertson, R. Robie, F. Robinet, A. Rocchi, S. Rodriguez, L. Rolland, J. G. Rollins, M. Romanelli, R. Romano, C. L. Romel, A. Romero-Rodríguez, I. M. Romero-Shaw, J. H. Romie, S. Ronchini, L. Rosa, C. A. Rose, D. Rosińska, M. P. Ross, S. Rowan, S. J. Rowlinson, S. Roy, Santosh Roy, Soumen Roy, D. Rozza, P. Ruggi, K. Ruiz-Rocha, K. Ryan, S. Sachdev, T. Sadecki, J. Sadiq, N. Sago, S. Saito, Y. Saito, K. Sakai, Y. Sakai, M. Sakellariadou, Y. Sakuno, O. S. Salafia, L. Salconi, M. Saleem, F. Salemi, A. Samajdar, E. J. Sanchez, J. H. Sanchez, L. E. Sanchez, N. Sanchis-Gual, J. R. Sanders, A. Sanuy, T. R. Saravanan, N. Sarin, B. Sassolas, H. Satari, B. S. Sathyaprakash, S. Sato, T. Sato, O. Sauter, R. L. Savage, T. Sawada, D. Sawant, H. L. Sawant, S. Sayah, D. Schaetzl, M. Scheel, J. Scheuer, M. Schiworski, P. Schmidt, S. Schmidt, R. Schnabel, M. Schneewind, R. M. S. Schofield, A. Schönbeck, B. W. Schulte, B. F. Schutz, E. Schwartz, J. Scott, S. M. Scott, M. Seglar-Arroyo, T. Sekiguchi, Y. Sekiguchi, D. Sellers, A. S. Sengupta, D. Sentenac, E. G. Seo, V. Sequino, A. Sergeev, Y. Setyawati, T. Shaffer, M. S. Shahriar, B. Shams, L. Shao, A. Sharma, P. Sharma, P. Shawhan, N. S. Shcheblanov, S. Shibagaki, M. Shikauchi, R. Shimizu, T. Shimoda, K. Shimode, H. Shinkai, T. Shishido, A. Shoda, D. H. Shoemaker, D. M. Shoemaker, S. ShyamSundar, M. Sieniawska, D. Sigg, L. P. Singer, D. Singh, N. Singh, A. Singha, A. M. Sintes, V. Sipala, V. Skliris, B. J. J. Slagmolen, T. J. Slaven-Blair, J. Smetana, J. R. Smith, R. J. E. Smith, J. Soldateschi, S. N. Somala, K. Somiya, E. J. Son, K. Soni, S. Soni, V. Sordini, F. Sorrentino, N. Sorrentino, H. Sotani, R. Soulard, T. Souradeep, E. Sowell, V. Spagnuolo, A. P. Spencer, M. Spera, R. Srinivasan, A. K. Srivastava, V. Srivastava, K. Staats, C. Stachie, D. A. Steer, J. Steinhoff, J. Steinlechner, S. Steinlechner, S. P. Stevenson, D. J. Stops, M. Stover, K. A. Strain, L. C. Strang, G. Stratta, A. Strunk, R. Sturani, A. L. Stuver, S. Sudhagar, V. Sudhir, R. Sugimoto, H. G. Suh, A. G. Sullivan, J. M. Sullivan, T. Z. Summerscales, H. Sun, L. Sun, S. Sunil, A. Sur, J. Suresh, P. J. Sutton, Takamasa Suzuki, Toshikazu Suzuki, B. L. Swinkels, M. J. Szczepańczyk, P. Szewczyk, M. Tacca, H. Tagoshi, S. C. Tait, H. Takahashi, R. Takahashi, A. Takamori, S. Takano, H. Takeda, M. Takeda, C. J. Talbot, C. Talbot, H. Tanaka, Kazuyuki Tanaka, Kenta Tanaka, Taiki Tanaka, Takahiro Tanaka, A. J. Tanasijczuk, S. Tanioka, D. B. Tanner, D. Tao, L. Tao, E. N. Tapia San Martín, C. Taranto, J. D. Tasson, S. Telada, R. Tenorio, J. E. Terhune, L. Terkowski, M. P. Thirugnanasambandam, L. Thomas, M. Thomas, P. Thomas, J. E. Thompson, S. R. Thondapu, K. A. Thorne, E. Thrane, Shubhanshu Tiwari, Srishti Tiwari, V. Tiwari, A. M. Toivonen, K. Toland, A. E. Tolley, T. Tomaru, Y. Tomigami, T. Tomura, M. Tonelli, A. Torres-Forné, C. I. Torrie, I. Tosta e Melo, D. Töyrä, A. Trapananti, F. Travasso, G. Traylor, M. Trevor, M. C. Tringali, A. Tripathee, L. Troiano, A. Trovato, L. Trozzo, R. J. Trudeau, D. S. Tsai, D. Tsai, K. W. Tsang, T. Tsang, J-S. Tsao, M. Tse, R. Tso, K. Tsubono, S. Tsuchida, L. Tsukada, D. Tsuna, T. Tsutsui, T. Tsuzuki, K. Turbang, M. Turconi, D. Tuyenbayev, A. S. Ubhi, N. Uchikata, T. Uchiyama, R. P. Udall, A. Ueda, T. Uehara, K. Ueno, G. Ueshima, C. S. Unnikrishnan, F. Uraguchi, A. L. Urban, T. Ushiba, A. Utina, H. Vahlbruch, G. Vajente, A. Vajpeyi, G. Valdes, M. Valentini, V. Valsan, N. van Bakel, M. van Beuzekom, J. F. J. van den Brand, C. Van Den Broeck, D. C. Vander-Hyde, L. van der Schaaf, J. V. van Heijningen, J. Vanosky, M. H. P. M. van Putten, N. van Remortel, M. Vardaro, A. F. Vargas, V. Varma, M. Vasúth, A. Vecchio, G. Vedovato, J. Veitch, P. J. Veitch, J. Venneberg, G. Venugopalan, D. Verkindt, P. Verma, Y. Verma, D. Veske, F. Vetrano, A. Viceré, S. Vidyant, A. D. Viets, A. Vijaykumar, V. Villa-Ortega, J.-Y. Vinet, A. Virtuoso, S. Vitale, T. Vo, H. Vocca, E. R. G. von Reis, J. S. A. von Wrangel, C. Vorvick, S. P. Vyatchanin, L. E. Wade, M. Wade, K. J. Wagner, R. C. Walet, M. Walker, G. S. Wallace, L. Wallace, S. Walsh, J. Wang, J. Z. Wang, W. H. Wang, R. L. Ward, J. Warner, M. Was, T. Washimi, N. Y. Washington, J. Watchi, B. Weaver, S. A. Webster, M. Weinert, A. J. Weinstein, R. Weiss, C. M. Weller, R. A. Weller, F. Wellmann, L. Wen, P. Weßels, K. Wette, J. T. Whelan, D. D. White, B. F. Whiting, C. Whittle, D. Wilken, D. Williams, M. J. Williams, N. Williams, A. R. Williamson, J. L. Willis, B. Willke, D. J. Wilson, W. Winkler, C. C. Wipf, T. Wlodarczyk, G. Woan, J. Woehler, J. K. Wofford, I. C. F. Wong, C. Wu, D. S. Wu, H. Wu, S. Wu, D. M. Wysocki, L. Xiao, W-R. Xu, T. Yamada, H. Yamamoto, Kazuhiro Yamamoto, Kohei Yamamoto, T. Yamamoto, K. Yamashita, R. Yamazaki, F. W. Yang, L. Yang, Y. Yang, Yang Yang, Z. Yang, M. J. Yap, D. W. Yeeles, A. B. Yelikar, M. Ying, K. Yokogawa, J. Yokoyama, T. Yokozawa, J. Yoo, T. Yoshioka, Hang Yu, Haocun Yu, H. Yuzurihara, A Zadrożny, M. Zanolin, S. Zeidler, T. Zelenova, J.-P. Zendri, M. Zevin, M. Zhan, H. Zhang, J. Zhang, L. Zhang, T. Zhang, Y. Zhang, C. Zhao, G. Zhao, Y. Zhao, Yue Zhao, Y. Zheng, R. Zhou, Z. Zhou, X. J. Zhu, Z.-H. Zhu, A. B. Zimmerman, Y. Zlochower, M. E. Zucker, and J. Zweizig

Subjects
Physics, QC1-999
Abstract

The third Gravitational-Wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15∶00 Coordinated Universal Time (UTC) and 27 March 2020, 17∶00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin p_{astro}>0.5. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with p_{astro}>0.5 are consistent with gravitational-wave signals from binary black holes or neutron-star–black-hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron-star–black-hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with p_{astro}>0.5 across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars.

Published
2023
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23. Editorial: Plant RNA structure

Author

Huakun Zhang, Betty Y.-W. Chung, Zhiye Wang, and Yiliang Ding

Subjects
RNA structure, internal ribosomal entry site activity, in vivo RNA structure probing, thermoregulation, RNA G-quadruplex structure, plant growth and development, Plant culture, SB1-1110
Published
2023
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24. Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations

Author

Jennifer R. Habel, Brendon Y. Chua, Lukasz Kedzierski, Kevin J. Selva, Timon Damelang, Ebene R. Haycroft, Thi H.O. Nguyen, Hui-Fern Koay, Suellen Nicholson, Hayley A. McQuilten, Xiaoxiao Jia, Lilith F. Allen, Luca Hensen, Wuji Zhang, Carolien E. van de Sandt, Jessica A. Neil, Katherine Pragastis, Jillian S.Y. Lau, Jaycee Jumarang, E. Kaitlynn Allen, Fatima Amanant, Florian Krammer, Kathleen M. Wragg, Jennifer A. Juno, Adam K. Wheatley, Hyon-Xhi Tan, Gabrielle Pell, Susan Walker, Jennifer Audsley, Arnold Reynaldi, Irani Thevarajan, Justin T. Denholm, Kanta Subbarao, Miles P. Davenport, P. Mark Hogarth, Dale I. Godfrey, Allen C. Cheng, Steven Y.C. Tong, Katherine Bond, Deborah A. Williamson, James H. McMahon, Paul G. Thomas, Pia S. Pannaraj, Fiona James, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano, Claire L. Gordon, Amy W. Chung, Clare L. Whitehead, Stephen J. Kent, Martha Lappas, Louise C. Rowntree, and Katherine Kedzierska

Subjects
Immunology, Infectious disease, Medicine
Abstract

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2–infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.

Published
2023
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25. Leukocyte Telomere Length and Childhood Onset of Systemic Lupus Erythematosus in the Black Women's Experiences Living with Lupus Study

Author

John Bridges, Kara W. Chung, Connor D. Martz, Emily A. Smitherman, Cristina Drenkard, Calvin Wu, Jue Lin, S. Sam Lim, and David H. Chae

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Objective The study objective was to compare leukocyte telomere length (LTL) among patients with systemic lupus erythematosus (SLE) diagnosed in childhood versus adulthood. Methods Data are from the Black Women's Experiences Living with Lupus (BeWELL) study. Multivariable linear regression analyses that examined childhood diagnosis of SLE (diagnosed before 18 years of age), age, and their interaction in relationship to LTL were conducted, adjusting for a range of demographic, socioeconomic, and health‐related covariates. Results The total analytic sample size was 415. Forty participants (9.6%) were diagnosed in childhood. There was no main effect of childhood diagnosis on LTL (b = 0.007; 95% confidence interval [CI]: −0.089 to 0.103). However, the interaction between age and childhood diagnosis was significant (b = −0.008; 95% CI: −0.016 to −0.001), indicating a steeper inverse association between age and LTL among those diagnosed in childhood compared with those diagnosed in adulthood. This interaction remained statistically significant (P = 0.024) after controlling for disease duration measured dichotomously (less than 10 years vs. 10 years or more); it was marginally significant (P = 0.083) when controlling for disease duration measured continuously. Conclusion This cross‐sectional analysis suggests that Black women with childhood‐onset SLE may undergo accelerated LTL shortening compared with their adult‐onset counterparts. This relationship persisted even after controlling for differences in SLE damage and disease duration. These findings inform research on immunosenescence mechanisms of SLE.

Published
2022
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26. SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity

Author

Wuji Zhang, Brendon Y. Chua, Kevin J. Selva, Lukasz Kedzierski, Thomas M. Ashhurst, Ebene R. Haycroft, Suzanne K. Shoffner-Beck, Luca Hensen, David F. Boyd, Fiona James, Effie Mouhtouris, Jason C. Kwong, Kyra Y. L. Chua, George Drewett, Ana Copaescu, Julie E. Dobson, Louise C. Rowntree, Jennifer R. Habel, Lilith F. Allen, Hui-Fern Koay, Jessica A. Neil, Matthew J. Gartner, Christina Y. Lee, Patiyan Andersson, Sadid F. Khan, Luke Blakeway, Jessica Wisniewski, James H. McMahon, Erica E. Vine, Anthony L. Cunningham, Jennifer Audsley, Irani Thevarajan, Torsten Seemann, Norelle L. Sherry, Fatima Amanat, Florian Krammer, Sarah L. Londrigan, Linda M. Wakim, Nicholas J. C. King, Dale I. Godfrey, Laura K. Mackay, Paul G. Thomas, Suellen Nicholson, Kelly B. Arnold, Amy W. Chung, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano, Claire L. Gordon, Thi H. O. Nguyen, and Katherine Kedzierska

Subjects
Science
Abstract

The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.

Published
2022
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27. Tocilizumab overcomes chemotherapy resistance in mesenchymal stem-like breast cancer by negating autocrine IL-1A induction of IL-6

Author

Andrew W. Chung, Anthony J. Kozielski, Wei Qian, Jianying Zhou, Ann C. Anselme, Alfred A. Chan, Ping-Ying Pan, Delphine J. Lee, and Jenny C. Chang

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Triple-negative breast cancer (TNBC) patients with mesenchymal stem-like (MSL) subtype have responded poorly to chemotherapy whereas patients with basal-like 1 (BL1) subtype achieved the best clinical response. In order to gain insight into pathways that may contribute to the divergent sensitivity to chemotherapy, we compared the inflammatory profile of the two TNBC subtypes treated with docetaxel. Cellular signaling analysis determined that docetaxel activated MAPK pathway in MSL TNBCs but not BL1 TNBCs. The subsequent MAPK pathway activation in MSL TNBCs led to an IL-1A mediated cascade of autocrine inflammatory mediators including IL-6. Utilizing the humanized IL-6R antibody, tocilizumab, our in vitro and in vivo data show that MSL TNBCs treated with tocilizumab together with chemotherapy results in delayed tumor progression compared to MSL TNBCs treated with docetaxel alone. Our study highlights a molecular subset of TNBC that may be responsive to tocilizumab therapy for potential translational impact.

Published
2022
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28. Uncovering Examples of Humanizing Praxis and Pathological Violence in Special Education: District, Parent, and Researcher Perspectives

Author

Andy W. Chung

Abstract

Students of color continue to be labeled with dis/abilities and funneled into segregated settings by special education staff (Annamma, Connor, & Ferri, 2013; Leonardo & Broderick, 2011). The purpose of this study is to highlight the kinds of experiences students and their family's experience in special education related to humanization and violence. In addition to gaining a better understanding of how special education district staff are working to both reproduce and disrupt the violent exclusion of students of color, this dissertation aimed to center the experiences of parents and students who are being impacted by the exclusionary policies and practices. Using Disability Studies and Critical Race Theory (DisCrit) as a theoretical framework reminds educators that the term disproportionality is a euphemism for the state-sanctioned racist and ableist systemic violence students and parents experience (Artiles et al., 2010). Data was collected through narrative interviews with parents, teachers, and district staff as well as through personal reflections. Participants shared examples of violence dis/abled students experience in schools, ways parents are disregarded, and how school districts continue to disinvest in students and families of color. This study terms their experiences as examples of the kinds of "pathological violence" that are enacted within special education. What also surfaced were examples of critical educators implementing humanizing praxis, which is not often discussed or found in the field of special education. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2020

29. Antibody glycosylation correlates with disease progression in SIV‐Mycobacterium tuberculosis coinfected cynomolgus macaques

Author

Ebene R Haycroft, Timon Damelang, Ester Lopez, Mark A Rodgers, Bruce D Wines, Mark Hogarth, Cassaundra L Ameel, Stephen J Kent, Charles A Scanga, Shelby L O'Connor, and Amy W Chung

Subjects
antibodies, cynomolgus macaques, Fc, glycosylation, SIV, tuberculosis, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Tuberculosis (TB) remains a substantial cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) worldwide. However, the immunological mechanisms associated with the enhanced susceptibility among HIV‐positive individuals remain largely unknown. Methods Here, we used a simian immunodeficiency virus (SIV)/TB‐coinfection Mauritian cynomolgus macaque (MCM) model to examine humoral responses from the plasma of SIV‐negative (n = 8) and SIV‐positive (n = 7) MCM 8‐week postinfection with Mycobacterium tuberculosis (Mtb). Results Antibody responses to Mtb were impaired during SIV coinfection. Elevated inflammatory bulk IgG antibody glycosylation patterns were observed in coinfected macaques early at 8‐week post‐Mtb infection, including increased agalactosylation (G0) and reduced di‐galactosylation (G2), which correlated with endpoint Mtb bacterial burden and gross pathology scores, as well as the time‐to‐necropsy. Conclusion These studies suggest that humoral immunity may contribute to control of TB disease and support growing literature that highlights antibody Fc glycosylation as a biomarker of TB disease progression.

Published
2023
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30. Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity

Author

Wuji Zhang, Louise C Rowntree, Ramona Muttucumaru, Timon Damelang, Malet Aban, Aeron C Hurt, Maria Auladell, Robyn Esterbauer, Bruce Wines, Mark Hogarth, Stephen J Turner, Adam K Wheatley, Stephen J Kent, Sushrut Patil, Sharon Avery, Orla Morrissey, Amy W Chung, Marios Koutsakos, Thi HO Nguyen, Allen C Cheng, Tom C Kotsimbos, and Katherine Kedzierska

Subjects
antibodies, antibody landscapes, B cells, haematopoietic stem cell transplant recipients, influenza vaccination, system serology, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Influenza causes significant morbidity and mortality, especially in high‐risk populations. Although current vaccination regimens are the best method to combat annual influenza disease, vaccine efficacy can be low in high‐risk groups, such as haematopoietic stem cell transplant (HSCT) recipients. Methods We comprehensively assessed humoral immunity, antibody landscapes, systems serology and influenza‐specific B‐cell responses, together with their phenotypes and isotypes, to the inactivated influenza vaccine (IIV) in HSCT recipients in comparison to healthy controls. Results Inactivated influenza vaccine significantly increased haemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. Systems serology revealed increased IgG1 and IgG3 antibody levels towards the haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased frequencies of total, IgG class‐switched and CD21loCD27+ influenza‐specific B cells, determined by HA probes and flow cytometry. Strikingly, 40% of HSCT recipients had markedly higher antibody responses towards A/H3N2 vaccine strain than healthy controls and showed cross‐reactivity to antigenically drifted A/H3N2 strains by antibody landscape analysis. These superior humoral responses were associated with a greater time interval after HSCT, while multivariant analyses revealed the importance of pre‐existing immune memory. Conversely, in HSCT recipients who did not respond to the first dose, the second IIV dose did not greatly improve their humoral response, although 50% of second‐dose patients reached a seroprotective HAI titre for at least one of vaccine strains. Conclusions Our study demonstrates efficient, although time‐dependent, immune responses to IIV in HSCT recipients, and provides insights into influenza vaccination strategies targeted to immunocompromised high‐risk groups.

Published
2023
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31. Corrigendum: Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

Author

Bruce D. Wines, Liriye Kurtovic, Halina M. Trist, Sandra Esparon, Ester Lopez, Klasina Chappin, Li-Jin Chan, Francesca L. Mordant, Wen Shi Lee, Nicholas A. Gherardin, Sheila K. Patel, Gemma E. Hartley, Phillip Pymm, James P. Cooney, James G. Beeson, Dale I. Godfrey, Louise M. Burrell, Menno C. van Zelm, Adam K. Wheatley, Amy W. Chung, Wai-Hong Tham, Kanta Subbarao, Stephen J. Kent, and P. Mark Hogarth

Subjects
coronavirus, SARS-CoV-2, COVID-19, ACE2-Fc, neutralization, antibody effector function, Immunologic diseases. Allergy, RC581-607
Published
2023
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35. Chemically driven energetic molecular ferroelectrics

Author

Yong Hu, Zhiyu Liu, Chi-Chin Wu, Jennifer L. Gottfried, Rose Pesce-Rodriguez, Scott D. Walck, Peter W. Chung, and Shenqiang Ren

Subjects
Science
Abstract

An interest arises if energetic molecules and molecular ferroelectrics can be integrated together to obtain a chemically driven electricity conversion. Here, the authors explore energetic molecular ferroelectrics consisting of imidazolium cations and perchlorate anions with a high-power density.

Published
2021
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36. Biparatopic nanobodies targeting the receptor binding domain efficiently neutralize SARS-CoV-2

Author

Phillip Pymm, Samuel J. Redmond, Olan Dolezal, Francesca Mordant, Ester Lopez, James P. Cooney, Kathryn C. Davidson, Ebene R. Haycroft, Chee Wah Tan, Rebecca Seneviratna, Samantha L. Grimley, Damian F.J. Purcell, Stephen J. Kent, Adam K. Wheatley, Lin-Fa Wang, Andrew Leis, Alisa Glukhova, Marc Pellegrini, Amy W. Chung, Kanta Subbarao, Adam P. Uldrich, Wai-Hong Tham, Dale I. Godfrey, and Nicholas A. Gherardin

Subjects
Immunology, microbiology, structural biology, Science
Abstract

Summary: The development of therapeutics to prevent or treat COVID-19 remains an area of intense focus. Protein biologics, including monoclonal antibodies and nanobodies that neutralize virus, have potential for the treatment of active disease. Here, we have used yeast display of a synthetic nanobody library to isolate nanobodies that bind the receptor-binding domain (RBD) of SARS-CoV-2 and neutralize the virus. We show that combining two clones with distinct binding epitopes within the RBD into a single protein construct to generate biparatopic reagents dramatically enhances their neutralizing capacity. Furthermore, the biparatopic nanobodies exhibit enhanced control over clinically relevant RBD variants that escaped recognition by the individual nanobodies. Structural analysis of biparatopic binding to spike (S) protein revealed a unique binding mode whereby the two nanobody paratopes bridge RBDs encoded by distinct S trimers. Accordingly, biparatopic nanobodies offer a way to rapidly generate powerful viral neutralizers with enhanced ability to control viral escape mutants.

Published
2022
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37. Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques.

Author

Brendon Y Chua, Toshiki Sekiya, Marios Koutsakos, Naoki Nomura, Louise C Rowntree, Thi H O Nguyen, Hayley A McQuilten, Marumi Ohno, Yuki Ohara, Tomohiro Nishimura, Masafumi Endo, Yasushi Itoh, Jennifer R Habel, Kevin J Selva, Adam K Wheatley, Bruce D Wines, P Mark Hogarth, Stephen J Kent, Amy W Chung, David C Jackson, Lorena E Brown, Masashi Shingai, Katherine Kedzierska, and Hiroshi Kida

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their efficacy can be modest, especially in immunologically-naïve individuals. We investigated immune responses towards inactivated whole influenza virus particle vaccine (WPV) formulations, predicated to be more immunogenic, in a non-human primate model, as an important step towards clinical testing in humans. Comprehensive analyses were used to capture 46 immune parameters to profile how WPV-induced responses differed to those elicited by antigenically-similar SV formulations. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV consistently induced stronger antibody responses and hemagglutination inhibition (HI) antibody titres against vaccine-matched viruses compared to SV formulations, while acute reactogenic effects were similar. Responses in WPV-primed animals were further increased by boosting with the same formulation, conversely to modest responses after priming and boosting with SV. 28-parameter multiplex bead array defined key antibody features and showed that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV increased IgG responses against A/H1N1 hemagglutinin (HA) and HA-Stem, and higher IgA responses to A/H1N1-HA after each vaccine dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were also present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. Furthermore, WPV-enhanced antibody responses were associated with higher frequencies of HA-specific B-cells and IFN-γ-producing CD4+ T-cell responses. Our data additionally demonstrate stronger boosting of HI titres by WPV following prior infection and support WPV administered as a priming dose irrespective of the follow up vaccine for the second dose. Our findings thus show that compared to SV vaccination, WPV-induced humoral responses are significantly increased in scope and magnitude, advocating WPV vaccination regimens for priming immunologically-naïve individuals and also in the event of a pandemic outbreak.

Published
2022
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38. RNA structure mediated thermoregulation: What can we learn from plants?

Author

Sherine E. Thomas, Martin Balcerowicz, and Betty Y.-W. Chung

Subjects
RNA structure, plants, translation, protein synthesis, thermosensor, temperature, Plant culture, SB1-1110
Abstract

RNA molecules have the capacity to form a multitude of distinct secondary and tertiary structures, but only the most energetically favorable conformations are adopted at any given time. Formation of such structures strongly depends on the environment and consequently, these structures are highly dynamic and may refold as their surroundings change. Temperature is one of the most direct physical parameters that influence RNA structure dynamics, and in turn, thermosensitive RNA structures can be harnessed by a cell to perceive and respond to its temperature environment. Indeed, many thermosensitive RNA structures with biological function have been identified in prokaryotic organisms, but for a long time such structures remained elusive in eukaryotes. Recent discoveries, however, reveal that thermosensitive RNA structures are also found in plants, where they affect RNA stability, pre-mRNA splicing and translation efficiency in a temperature-dependent manner. In this minireview, we provide a short overview of thermosensitive RNA structures in prokaryotes and eukaryotes, highlight recent advances made in identifying such structures in plants and discuss their similarities and differences to established prokaryotic RNA thermosensors.

Published
2022
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39. Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

Author

Bruce D. Wines, Liriye Kurtovic, Halina M. Trist, Sandra Esparon, Ester Lopez, Klasina Chappin, Li-Jin Chan, Francesca L. Mordant, Wen Shi Lee, Nicholas A. Gherardin, Sheila K. Patel, Gemma E. Hartley, Phillip Pymm, James P. Cooney, James G. Beeson, Dale I. Godfrey, Louise M. Burrell, Menno C. van Zelm, Adam K. Wheatley, Amy W. Chung, Wai-Hong Tham, Kanta Subbarao, Stephen J. Kent, and P. Mark Hogarth

Subjects
coronavirus, SARS-CoV-2, COVID-19, ACE2-Fc, neutralization, antibody effector function, Immunologic diseases. Allergy, RC581-607
Abstract

Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins, formatted with or without the ACE2 collectrin domain, were optimized by Fc-modification. The different Fc-modifications resulted in distinct effects on neutralization and effector functions. H429Y, a point mutation outside the binding sites for FcγRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcγR interaction and enhanced SARS-CoV-2 neutralization. Another Fc mutation, H429F did not improve virus neutralization but resulted in increased C5b-C9 fixation and transformed ACE2-Fc to a potent mediator of complement-dependent cytotoxicity (CDC) against SARS-CoV-2 spike (S) expressing cells. Furthermore, modification of the Fc-glycan enhanced cell activation via FcγRIIIa. These different immune profiles demonstrate the capacity of Fc-based agents to be engineered to optimize different mechanisms of protection for SARS-CoV-2 and potentially other viral pathogens.

Published
2022
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40. Ena/VASP Protein-Mediated Actin Polymerization Contributes to Naïve CD8+ T Cell Activation and Expansion by Promoting T Cell–APC Interactions In Vivo

Author

Monique M. Waldman, Jeremy T. Rahkola, Ashton L. Sigler, Jeffrey W. Chung, Benjamin A. S. Willett, Ross M. Kedl, Rachel S. Friedman, and Jordan Jacobelli

Subjects
T cell, cytoskeleton, VASP, T cell activation, T cell motility, two-photon microscopy, Immunologic diseases. Allergy, RC581-607
Abstract

Naïve T cell activation in secondary lymphoid organs such as lymph nodes (LNs) occurs upon recognition of cognate antigen presented by antigen presenting cells (APCs). T cell activation requires cytoskeleton rearrangement and sustained interactions with APCs. Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are a family of cytoskeletal effector proteins responsible for actin polymerization and are frequently found at the leading edge of motile cells. Ena/VASP proteins have been implicated in motility and adhesion in various cell types, but their role in primary T cell interstitial motility and activation has not been explored. Our goal was to determine the contribution of Ena/VASP proteins to T cell–APC interactions, T cell activation, and T cell expansion in vivo. Our results showed that naïve T cells from Ena/VASP-deficient mice have a significant reduction in antigen-specific T cell accumulation following Listeria monocytogenes infection. The kinetics of T cell expansion impairment were further confirmed in Ena/VASP-deficient T cells stimulated via dendritic cell immunization. To investigate the cause of this T cell expansion defect, we analyzed T cell–APC interactions in vivo by two-photon microscopy and observed fewer Ena/VASP-deficient naïve T cells interacting with APCs in LNs during priming. We also determined that Ena/VASP-deficient T cells formed conjugates with significantly less actin polymerization at the T cell–APC synapse, and that these conjugates were less stable than their WT counterparts. Finally, we found that Ena/VASP-deficient T cells have less LFA-1 polarized to the T cell–APC synapse. Thus, we conclude that Ena/VASP proteins contribute to T cell actin remodeling during T cell–APC interactions, which promotes the initiation of stable T cell conjugates during APC scanning. Therefore, Ena/VASP proteins are required for efficient activation and expansion of T cells in vivo.

Published
2022
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41. Systems serology detects functionally distinct coronavirus antibody features in children and elderly

Author

Kevin J. Selva, Carolien E. van de Sandt, Melissa M. Lemke, Christina Y. Lee, Suzanne K. Shoffner, Brendon Y. Chua, Samantha K. Davis, Thi H. O. Nguyen, Louise C. Rowntree, Luca Hensen, Marios Koutsakos, Chinn Yi Wong, Francesca Mordant, David C. Jackson, Katie L. Flanagan, Jane Crowe, Shidan Tosif, Melanie R. Neeland, Philip Sutton, Paul V. Licciardi, Nigel W. Crawford, Allen C. Cheng, Denise L. Doolan, Fatima Amanat, Florian Krammer, Keith Chappell, Naphak Modhiran, Daniel Watterson, Paul Young, Wen Shi Lee, Bruce D. Wines, P. Mark Hogarth, Robyn Esterbauer, Hannah G. Kelly, Hyon-Xhi Tan, Jennifer A. Juno, Adam K. Wheatley, Stephen J. Kent, Kelly B. Arnold, Katherine Kedzierska, and Amy W. Chung

Subjects
Science
Abstract

Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Published
2021
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42. Population of Merging Compact Binaries Inferred Using Gravitational Waves through GWTC-3

Author

R. Abbott, T. D. Abbott, F. Acernese, K. Ackley, C. Adams, N. Adhikari, R. X. Adhikari, V. B. Adya, C. Affeldt, D. Agarwal, M. Agathos, K. Agatsuma, N. Aggarwal, O. D. Aguiar, L. Aiello, A. Ain, P. Ajith, T. Akutsu, P. F. de Alarcón, S. Akcay, S. Albanesi, A. Allocca, P. A. Altin, A. Amato, C. Anand, S. Anand, A. Ananyeva, S. B. Anderson, W. G. Anderson, M. Ando, T. Andrade, N. Andres, T. Andrić, S. V. Angelova, S. Ansoldi, J. M. Antelis, S. Antier, F. Antonini, S. Appert, Koji Arai, Koya Arai, Y. Arai, S. Araki, A. Araya, M. C. Araya, J. S. Areeda, M. Arène, N. Aritomi, N. Arnaud, M. Arogeti, S. M. Aronson, K. G. Arun, H. Asada, Y. Asali, G. Ashton, Y. Aso, M. Assiduo, S. M. Aston, P. Astone, F. Aubin, C. Austin, S. Babak, F. Badaracco, M. K. M. Bader, C. Badger, S. Bae, Y. Bae, A. M. Baer, S. Bagnasco, Y. Bai, L. Baiotti, J. Baird, R. Bajpai, M. Ball, G. Ballardin, S. W. Ballmer, A. Balsamo, G. Baltus, S. Banagiri, D. Bankar, J. C. Barayoga, C. Barbieri, B. C. Barish, D. Barker, P. Barneo, F. Barone, B. Barr, L. Barsotti, M. Barsuglia, D. Barta, J. Bartlett, M. A. Barton, I. Bartos, R. Bassiri, A. Basti, M. Bawaj, J. C. Bayley, A. C. Baylor, M. Bazzan, B. Bécsy, V. M. Bedakihale, M. Bejger, I. Belahcene, V. Benedetto, D. Beniwal, T. F. Bennett, J. D. Bentley, M. BenYaala, F. Bergamin, B. K. Berger, S. Bernuzzi, C. P. L. Berry, D. Bersanetti, A. Bertolini, J. Betzwieser, D. Beveridge, R. Bhandare, U. Bhardwaj, D. Bhattacharjee, S. Bhaumik, I. A. Bilenko, G. Billingsley, S. Bini, R. Birney, O. Birnholtz, S. Biscans, M. Bischi, S. Biscoveanu, A. Bisht, B. Biswas, M. Bitossi, M.-A. Bizouard, J. K. Blackburn, C. D. Blair, D. G. Blair, R. M. Blair, F. Bobba, N. Bode, M. Boer, G. Bogaert, M. Boldrini, L. D. Bonavena, F. Bondu, E. Bonilla, R. Bonnand, P. Booker, B. A. Boom, R. Bork, V. Boschi, N. Bose, S. Bose, V. Bossilkov, V. Boudart, Y. Bouffanais, A. Bozzi, C. Bradaschia, P. R. Brady, A. Bramley, A. Branch, M. Branchesi, J. Brandt, J. E. Brau, M. Breschi, T. Briant, J. H. Briggs, A. Brillet, M. Brinkmann, P. Brockill, A. F. Brooks, J. Brooks, D. D. Brown, S. Brunett, G. Bruno, R. Bruntz, J. Bryant, T. Bulik, H. J. Bulten, A. Buonanno, R. Buscicchio, D. Buskulic, C. Buy, R. L. Byer, L. Cadonati, G. Cagnoli, C. Cahillane, J. Calderón Bustillo, J. D. Callaghan, T. A. Callister, E. Calloni, J. Cameron, J. B. Camp, M. Canepa, S. Canevarolo, M. Cannavacciuolo, K. C. Cannon, H. Cao, Z. Cao, E. Capocasa, E. Capote, G. Carapella, F. Carbognani, J. B. Carlin, M. F. Carney, M. Carpinelli, G. Carrillo, G. Carullo, T. L. Carver, J. Casanueva Diaz, C. Casentini, G. Castaldi, S. Caudill, M. Cavaglià, F. Cavalier, R. Cavalieri, M. Ceasar, G. Cella, P. Cerdá-Durán, E. Cesarini, W. Chaibi, K. Chakravarti, S. Chalathadka Subrahmanya, E. Champion, C.-H. Chan, C. Chan, C. L. Chan, K. Chan, M. Chan, K. Chandra, P. Chanial, S. Chao, C. E. A. Chapman-Bird, P. Charlton, E. A. Chase, E. Chassande-Mottin, C. Chatterjee, Debarati Chatterjee, Deep Chatterjee, M. Chaturvedi, S. Chaty, K. Chatziioannou, C. Chen, H. Y. Chen, J. Chen, K. Chen, X. Chen, Y.-B. Chen, Y.-R. Chen, Z. Chen, H. Cheng, C. K. Cheong, H. Y. Cheung, H. Y. Chia, F. Chiadini, C-Y. Chiang, G. Chiarini, R. Chierici, A. Chincarini, M. L. Chiofalo, A. Chiummo, G. Cho, H. S. Cho, R. K. Choudhary, S. Choudhary, N. Christensen, H. Chu, Q. Chu, Y-K. Chu, S. Chua, K. W. Chung, G. Ciani, P. Ciecielag, M. Cieślar, M. Cifaldi, A. A. Ciobanu, R. Ciolfi, F. Cipriano, A. Cirone, F. Clara, E. N. Clark, J. A. Clark, L. Clarke, P. Clearwater, S. Clesse, F. Cleva, E. Coccia, E. Codazzo, P.-F. Cohadon, D. E. Cohen, L. Cohen, M. Colleoni, C. G. Collette, A. Colombo, M. Colpi, C. M. Compton, M. Constancio, Jr., L. Conti, S. J. Cooper, P. Corban, T. R. Corbitt, I. Cordero-Carrión, S. Corezzi, K. R. Corley, N. Cornish, D. Corre, A. Corsi, S. Cortese, C. A. Costa, R. Cotesta, M. W. Coughlin, J.-P. Coulon, S. T. Countryman, B. Cousins, P. Couvares, D. M. Coward, M. J. Cowart, D. C. Coyne, R. Coyne, J. D. E. Creighton, T. D. Creighton, A. W. Criswell, M. Croquette, S. G. Crowder, J. R. Cudell, T. J. Cullen, A. Cumming, R. Cummings, L. Cunningham, E. Cuoco, M. Curyło, P. Dabadie, T. Dal Canton, S. Dall’Osso, G. Dálya, A. Dana, L. M. DaneshgaranBajastani, B. D’Angelo, B. Danila, S. Danilishin, S. D’Antonio, K. Danzmann, C. Darsow-Fromm, A. Dasgupta, L. E. H. Datrier, S. Datta, V. Dattilo, I. Dave, M. Davier, G. S. Davies, D. Davis, M. C. Davis, E. J. Daw, R. Dean, D. DeBra, M. Deenadayalan, J. Degallaix, M. De Laurentis, S. Deléglise, V. Del Favero, F. De Lillo, N. De Lillo, W. Del Pozzo, L. M. DeMarchi, F. De Matteis, V. D’Emilio, N. Demos, T. Dent, A. Depasse, R. De Pietri, R. De Rosa, C. De Rossi, R. DeSalvo, R. De Simone, S. Dhurandhar, M. C. Díaz, M. Diaz-Ortiz, Jr., N. A. Didio, T. Dietrich, L. Di Fiore, C. Di Fronzo, C. Di Giorgio, F. Di Giovanni, M. Di Giovanni, T. Di Girolamo, A. Di Lieto, B. Ding, S. Di Pace, I. Di Palma, F. Di Renzo, A. K. Divakarla, A. Dmitriev, Z. Doctor, L. D’Onofrio, F. Donovan, K. L. Dooley, S. Doravari, I. Dorrington, M. Drago, J. C. Driggers, Y. Drori, J.-G. Ducoin, P. Dupej, O. Durante, D. D’Urso, P.-A. Duverne, S. E. Dwyer, C. Eassa, P. J. Easter, M. Ebersold, T. Eckhardt, G. Eddolls, B. Edelman, T. B. Edo, O. Edy, A. Effler, S. Eguchi, J. Eichholz, S. S. Eikenberry, M. Eisenmann, R. A. Eisenstein, A. Ejlli, E. Engelby, Y. Enomoto, L. Errico, R. C. Essick, H. Estellés, D. Estevez, Z. Etienne, T. Etzel, M. Evans, T. M. Evans, B. E. Ewing, V. Fafone, H. Fair, S. Fairhurst, A. M. Farah, S. Farinon, B. Farr, W. M. Farr, N. W. Farrow, E. J. Fauchon-Jones, G. Favaro, M. Favata, M. Fays, M. Fazio, J. Feicht, M. M. Fejer, E. Fenyvesi, D. L. Ferguson, A. Fernandez-Galiana, I. Ferrante, T. A. Ferreira, F. Fidecaro, P. Figura, I. Fiori, M. Fishbach, R. P. Fisher, R. Fittipaldi, V. Fiumara, R. Flaminio, E. Floden, H. Fong, J. A. Font, B. Fornal, P. W. F. Forsyth, A. Franke, S. Frasca, F. Frasconi, C. Frederick, J. P. Freed, Z. Frei, A. Freise, R. Frey, P. Fritschel, V. V. Frolov, G. G. Fronzé, Y. Fujii, Y. Fujikawa, M. Fukunaga, M. Fukushima, P. Fulda, M. Fyffe, H. A. Gabbard, B. U. Gadre, J. R. Gair, J. Gais, S. Galaudage, R. Gamba, D. Ganapathy, A. Ganguly, D. Gao, S. G. Gaonkar, B. Garaventa, F. García, C. García-Núñez, C. García-Quirós, F. Garufi, B. Gateley, S. Gaudio, V. Gayathri, G.-G. Ge, G. Gemme, A. Gennai, J. George, R. N. George, O. Gerberding, L. Gergely, P. Gewecke, S. Ghonge, Abhirup Ghosh, Archisman Ghosh, Shaon Ghosh, Shrobana Ghosh, B. Giacomazzo, L. Giacoppo, J. A. Giaime, K. D. Giardina, D. R. Gibson, C. Gier, M. Giesler, P. Giri, F. Gissi, J. Glanzer, A. E. Gleckl, P. Godwin, J. Golomb, E. Goetz, R. Goetz, N. Gohlke, B. Goncharov, G. González, A. Gopakumar, M. Gosselin, R. Gouaty, D. W. Gould, B. Grace, A. Grado, M. Granata, V. Granata, A. Grant, S. Gras, P. Grassia, C. Gray, R. Gray, G. Greco, A. C. Green, R. Green, A. M. Gretarsson, E. M. Gretarsson, D. Griffith, W. Griffiths, H. L. Griggs, G. Grignani, A. Grimaldi, S. J. Grimm, H. Grote, S. Grunewald, P. Gruning, D. Guerra, G. M. Guidi, A. R. Guimaraes, G. Guixé, H. K. Gulati, H.-K. Guo, Y. Guo, Anchal Gupta, Anuradha Gupta, P. Gupta, E. K. Gustafson, R. Gustafson, F. Guzman, S. Ha, L. Haegel, A. Hagiwara, S. Haino, O. Halim, E. D. Hall, E. Z. Hamilton, G. Hammond, W.-B. Han, M. Haney, J. Hanks, C. Hanna, M. D. Hannam, O. Hannuksela, H. Hansen, T. J. Hansen, J. Hanson, T. Harder, T. Hardwick, K. Haris, J. Harms, G. M. Harry, I. W. Harry, D. Hartwig, K. Hasegawa, B. Haskell, R. K. Hasskew, C.-J. Haster, K. Hattori, K. Haughian, H. Hayakawa, K. Hayama, F. J. Hayes, J. Healy, A. Heidmann, A. Heidt, M. C. Heintze, J. Heinze, J. Heinzel, H. Heitmann, F. Hellman, P. Hello, A. F. Helmling-Cornell, G. Hemming, M. Hendry, I. S. Heng, E. Hennes, J. Hennig, M. H. Hennig, A. G. Hernandez, F. Hernandez Vivanco, M. Heurs, S. Hild, P. Hill, Y. Himemoto, A. S. Hines, Y. Hiranuma, N. Hirata, E. Hirose, S. Hochheim, D. Hofman, J. N. Hohmann, D. G. Holcomb, N. A. Holland, I. J. Hollows, Z. J. Holmes, K. Holt, D. E. Holz, Z. Hong, P. Hopkins, J. Hough, S. Hourihane, E. J. Howell, C. G. Hoy, D. Hoyland, A. Hreibi, B-H. Hsieh, Y. Hsu, G-Z. Huang, H-Y. Huang, P. Huang, Y-C. Huang, Y.-J. Huang, Y. Huang, M. T. Hübner, A. D. Huddart, B. Hughey, D. C. Y. Hui, V. Hui, S. Husa, S. H. Huttner, R. Huxford, T. Huynh-Dinh, S. Ide, B. Idzkowski, A. Iess, B. Ikenoue, S. Imam, K. Inayoshi, C. Ingram, Y. Inoue, K. Ioka, M. Isi, K. Isleif, K. Ito, Y. Itoh, B. R. Iyer, K. Izumi, V. JaberianHamedan, T. Jacqmin, S. J. Jadhav, S. P. Jadhav, A. L. James, A. Z. Jan, K. Jani, J. Janquart, K. Janssens, N. N. Janthalur, P. Jaranowski, D. Jariwala, R. Jaume, A. C. Jenkins, K. Jenner, C. Jeon, M. Jeunon, W. Jia, H.-B. Jin, G. R. Johns, A. W. Jones, D. I. Jones, J. D. Jones, P. Jones, R. Jones, R. J. G. Jonker, L. Ju, P. Jung, k. Jung, J. Junker, V. Juste, K. Kaihotsu, T. Kajita, M. Kakizaki, C. V. Kalaghatgi, V. Kalogera, B. Kamai, M. Kamiizumi, N. Kanda, S. Kandhasamy, G. Kang, J. B. Kanner, Y. Kao, S. J. Kapadia, D. P. Kapasi, S. Karat, C. Karathanasis, S. Karki, R. Kashyap, M. Kasprzack, W. Kastaun, S. Katsanevas, E. Katsavounidis, W. Katzman, T. Kaur, K. Kawabe, K. Kawaguchi, N. Kawai, T. Kawasaki, F. Kéfélian, D. Keitel, J. S. Key, S. Khadka, F. Y. Khalili, S. Khan, E. A. Khazanov, N. Khetan, M. Khursheed, N. Kijbunchoo, C. Kim, J. C. Kim, J. Kim, K. Kim, W. S. Kim, Y.-M. Kim, C. Kimball, N. Kimura, M. Kinley-Hanlon, R. Kirchhoff, J. S. Kissel, N. Kita, H. Kitazawa, L. Kleybolte, S. Klimenko, A. M. Knee, T. D. Knowles, E. Knyazev, P. Koch, G. Koekoek, Y. Kojima, K. Kokeyama, S. Koley, P. Kolitsidou, M. Kolstein, K. Komori, V. Kondrashov, A. K. H. Kong, A. Kontos, N. Koper, M. Korobko, K. Kotake, M. Kovalam, D. B. Kozak, C. Kozakai, R. Kozu, V. Kringel, N. V. Krishnendu, A. Królak, G. Kuehn, F. Kuei, P. Kuijer, S. Kulkarni, A. Kumar, P. Kumar, Rahul Kumar, Rakesh Kumar, J. Kume, K. Kuns, C. Kuo, H-S. Kuo, Y. Kuromiya, S. Kuroyanagi, K. Kusayanagi, S. Kuwahara, K. Kwak, P. Lagabbe, D. Laghi, E. Lalande, T. L. Lam, A. Lamberts, M. Landry, P. Landry, B. B. Lane, R. N. Lang, J. Lange, B. Lantz, I. La Rosa, A. Lartaux-Vollard, P. D. Lasky, M. Laxen, A. Lazzarini, C. Lazzaro, P. Leaci, S. Leavey, Y. K. Lecoeuche, H. K. Lee, H. M. Lee, H. W. Lee, J. Lee, K. Lee, R. Lee, J. Lehmann, A. Lemaître, M. Leonardi, N. Leroy, N. Letendre, C. Levesque, Y. Levin, J. N. Leviton, K. Leyde, A. K. Y. Li, B. Li, J. Li, K. L. Li, T. G. F. Li, X. Li, C-Y. Lin, F-K. Lin, F-L. Lin, H. L. Lin, L. C.-C. Lin, F. Linde, S. D. Linker, J. N. Linley, T. B. Littenberg, G. C. Liu, J. Liu, K. Liu, X. Liu, F. Llamas, M. Llorens-Monteagudo, R. K. L. Lo, A. Lockwood, M. Loh, L. T. London, A. Longo, D. Lopez, M. Lopez Portilla, M. Lorenzini, V. Loriette, M. Lormand, G. Losurdo, T. P. Lott, J. D. Lough, C. O. Lousto, G. Lovelace, J. F. Lucaccioni, H. Lück, D. Lumaca, A. P. Lundgren, L.-W. Luo, J. E. Lynam, R. Macas, M. MacInnis, D. M. Macleod, I. A. O. MacMillan, A. Macquet, I. Magaña Hernandez, C. Magazzù, R. M. Magee, R. Maggiore, M. Magnozzi, S. Mahesh, E. Majorana, C. Makarem, I. Maksimovic, S. Maliakal, A. Malik, N. Man, V. Mandic, V. Mangano, J. L. Mango, G. L. Mansell, M. Manske, M. Mantovani, M. Mapelli, F. Marchesoni, M. Marchio, F. Marion, Z. Mark, S. Márka, Z. Márka, C. Markakis, A. S. Markosyan, A. Markowitz, E. Maros, A. Marquina, S. Marsat, F. Martelli, I. W. Martin, R. M. Martin, M. Martinez, V. A. Martinez, V. Martinez, K. Martinovic, D. V. Martynov, E. J. Marx, H. Masalehdan, K. Mason, E. Massera, A. Masserot, T. J. Massinger, M. Masso-Reid, S. Mastrogiovanni, A. Matas, M. Mateu-Lucena, F. Matichard, M. Matiushechkina, N. Mavalvala, J. J. McCann, R. McCarthy, D. E. McClelland, P. K. McClincy, S. McCormick, L. McCuller, G. I. McGhee, S. C. McGuire, C. McIsaac, J. McIver, T. McRae, S. T. McWilliams, D. Meacher, M. Mehmet, A. K. Mehta, Q. Meijer, A. Melatos, D. A. Melchor, G. Mendell, A. Menendez-Vazquez, C. S. Menoni, R. A. Mercer, L. Mereni, K. Merfeld, E. L. Merilh, J. D. Merritt, M. Merzougui, S. Meshkov, C. Messenger, C. Messick, P. M. Meyers, F. Meylahn, A. Mhaske, A. Miani, H. Miao, I. Michaloliakos, C. Michel, Y. Michimura, H. Middleton, L. Milano, A. L. Miller, A. Miller, B. Miller, S. Miller, M. Millhouse, J. C. Mills, E. Milotti, O. Minazzoli, Y. Minenkov, N. Mio, Ll. M. Mir, M. Miravet-Tenés, C. Mishra, T. Mishra, T. Mistry, S. Mitra, V. P. Mitrofanov, G. Mitselmakher, R. Mittleman, O. Miyakawa, A. Miyamoto, Y. Miyazaki, K. Miyo, S. Miyoki, Geoffrey Mo, L. M. Modafferi, E. Moguel, K. Mogushi, S. R. P. Mohapatra, S. R. Mohite, I. Molina, M. Molina-Ruiz, M. Mondin, M. Montani, C. J. Moore, D. Moraru, F. Morawski, A. More, C. Moreno, G. Moreno, Y. Mori, S. Morisaki, Y. Moriwaki, G. Morrás, B. Mours, C. M. Mow-Lowry, S. Mozzon, F. Muciaccia, Arunava Mukherjee, D. Mukherjee, Soma Mukherjee, Subroto Mukherjee, Suvodip Mukherjee, N. Mukund, A. Mullavey, J. Munch, E. A. Muñiz, P. G. Murray, R. Musenich, S. Muusse, S. L. Nadji, K. Nagano, S. Nagano, A. Nagar, K. Nakamura, H. Nakano, M. Nakano, R. Nakashima, Y. Nakayama, V. Napolano, I. Nardecchia, T. Narikawa, L. Naticchioni, B. Nayak, R. K. Nayak, R. Negishi, B. F. Neil, J. Neilson, G. Nelemans, T. J. N. Nelson, M. Nery, P. Neubauer, A. Neunzert, K. Y. Ng, S. W. S. Ng, C. Nguyen, P. Nguyen, T. Nguyen, L. Nguyen Quynh, W.-T. Ni, S. A. Nichols, A. Nishizawa, S. Nissanke, E. Nitoglia, F. Nocera, M. Norman, C. North, S. Nozaki, J. F. Nuño Siles, L. K. Nuttall, J. Oberling, B. D. O’Brien, Y. Obuchi, J. O’Dell, E. Oelker, W. Ogaki, G. Oganesyan, J. J. Oh, K. Oh, S. H. Oh, M. Ohashi, N. Ohishi, M. Ohkawa, F. Ohme, H. Ohta, M. A. Okada, Y. Okutani, K. Okutomi, C. Olivetto, K. Oohara, C. Ooi, R. Oram, B. O’Reilly, R. G. Ormiston, N. D. Ormsby, L. F. Ortega, R. O’Shaughnessy, E. O’Shea, S. Oshino, S. Ossokine, C. Osthelder, S. Otabe, D. J. Ottaway, H. Overmier, A. E. Pace, G. Pagano, M. A. Page, G. Pagliaroli, A. Pai, S. A. Pai, J. R. Palamos, O. Palashov, C. Palomba, H. Pan, K. Pan, P. K. Panda, H. Pang, P. T. H. Pang, C. Pankow, F. Pannarale, B. C. Pant, F. H. Panther, F. Paoletti, A. Paoli, A. Paolone, A. Parisi, H. Park, J. Park, W. Parker, D. Pascucci, A. Pasqualetti, R. Passaquieti, D. Passuello, M. Patel, M. Pathak, B. Patricelli, A. S. Patron, S. Paul, E. Payne, M. Pedraza, M. Pegoraro, A. Pele, F. E. Peña Arellano, S. Penn, A. Perego, A. Pereira, T. Pereira, C. J. Perez, C. Périgois, C. C. Perkins, A. Perreca, S. Perriès, J. Petermann, D. Petterson, H. P. Pfeiffer, K. A. Pham, K. S. Phukon, O. J. Piccinni, M. Pichot, M. Piendibene, F. Piergiovanni, L. Pierini, V. Pierro, G. Pillant, M. Pillas, F. Pilo, L. Pinard, I. M. Pinto, M. Pinto, B. Piotrzkowski, K. Piotrzkowski, M. Pirello, M. D. Pitkin, E. Placidi, L. Planas, W. Plastino, C. Pluchar, R. Poggiani, E. Polini, D. Y. T. Pong, S. Ponrathnam, P. Popolizio, E. K. Porter, R. Poulton, J. Powell, M. Pracchia, T. Pradier, A. K. Prajapati, K. Prasai, R. Prasanna, G. Pratten, M. Principe, G. A. Prodi, L. Prokhorov, P. Prosposito, L. Prudenzi, A. Puecher, M. Punturo, F. Puosi, P. Puppo, M. Pürrer, H. Qi, V. Quetschke, R. Quitzow-James, F. J. Raab, G. Raaijmakers, H. Radkins, N. Radulesco, P. Raffai, S. X. Rail, S. Raja, C. Rajan, K. E. Ramirez, T. D. Ramirez, A. Ramos-Buades, J. Rana, P. Rapagnani, U. D. Rapol, A. Ray, V. Raymond, N. Raza, M. Razzano, J. Read, L. A. Rees, T. Regimbau, L. Rei, S. Reid, S. W. Reid, D. H. Reitze, P. Relton, A. Renzini, P. Rettegno, A. Reza, M. Rezac, F. Ricci, D. Richards, J. W. Richardson, L. Richardson, G. Riemenschneider, K. Riles, S. Rinaldi, K. Rink, M. Rizzo, N. A. Robertson, R. Robie, F. Robinet, A. Rocchi, S. Rodriguez, L. Rolland, J. G. Rollins, M. Romanelli, R. Romano, C. L. Romel, A. Romero-Rodríguez, I. M. Romero-Shaw, J. H. Romie, S. Ronchini, L. Rosa, C. A. Rose, D. Rosińska, M. P. Ross, S. Rowan, S. J. Rowlinson, S. Roy, Santosh Roy, Soumen Roy, D. Rozza, P. Ruggi, K. Ryan, S. Sachdev, T. Sadecki, J. Sadiq, N. Sago, S. Saito, Y. Saito, K. Sakai, Y. Sakai, M. Sakellariadou, Y. Sakuno, O. S. Salafia, L. Salconi, M. Saleem, F. Salemi, A. Samajdar, E. J. Sanchez, J. H. Sanchez, L. E. Sanchez, N. Sanchis-Gual, J. R. Sanders, A. Sanuy, T. R. Saravanan, N. Sarin, B. Sassolas, H. Satari, B. S. Sathyaprakash, S. Sato, T. Sato, O. Sauter, R. L. Savage, T. Sawada, D. Sawant, H. L. Sawant, S. Sayah, D. Schaetzl, M. Scheel, J. Scheuer, M. Schiworski, P. Schmidt, S. Schmidt, R. Schnabel, M. Schneewind, R. M. S. Schofield, A. Schönbeck, B. W. Schulte, B. F. Schutz, E. Schwartz, J. Scott, S. M. Scott, M. Seglar-Arroyo, T. Sekiguchi, Y. Sekiguchi, D. Sellers, A. S. Sengupta, D. Sentenac, E. G. Seo, V. Sequino, A. Sergeev, Y. Setyawati, T. Shaffer, M. S. Shahriar, B. Shams, L. Shao, A. Sharma, P. Sharma, P. Shawhan, N. S. Shcheblanov, S. Shibagaki, M. Shikauchi, R. Shimizu, T. Shimoda, K. Shimode, H. Shinkai, T. Shishido, A. Shoda, D. H. Shoemaker, D. M. Shoemaker, S. ShyamSundar, M. Sieniawska, D. Sigg, L. P. Singer, D. Singh, N. Singh, A. Singha, A. M. Sintes, V. Sipala, V. Skliris, B. J. J. Slagmolen, T. J. Slaven-Blair, J. Smetana, J. R. Smith, R. J. E. Smith, J. Soldateschi, S. N. Somala, K. Somiya, E. J. Son, K. Soni, S. Soni, V. Sordini, F. Sorrentino, N. Sorrentino, H. Sotani, R. Soulard, T. Souradeep, E. Sowell, V. Spagnuolo, A. P. Spencer, M. Spera, R. Srinivasan, A. K. Srivastava, V. Srivastava, K. Staats, C. Stachie, D. A. Steer, J. Steinhoff, J. Steinlechner, S. Steinlechner, S. P. Stevenson, D. J. Stops, M. Stover, K. A. Strain, L. C. Strang, G. Stratta, A. Strunk, R. Sturani, A. L. Stuver, S. Sudhagar, V. Sudhir, R. Sugimoto, H. G. Suh, A. G. Sullivan, T. Z. Summerscales, H. Sun, L. Sun, S. Sunil, A. Sur, J. Suresh, P. J. Sutton, Takamasa Suzuki, Toshikazu Suzuki, B. L. Swinkels, M. J. Szczepańczyk, P. Szewczyk, M. Tacca, H. Tagoshi, S. C. Tait, H. Takahashi, R. Takahashi, A. Takamori, S. Takano, H. Takeda, M. Takeda, C. J. Talbot, C. Talbot, H. Tanaka, Kazuyuki Tanaka, Kenta Tanaka, Taiki Tanaka, Takahiro Tanaka, A. J. Tanasijczuk, S. Tanioka, D. B. Tanner, D. Tao, L. Tao, E. N. Tapia San Martín, C. Taranto, J. D. Tasson, S. Telada, R. Tenorio, J. E. Terhune, L. Terkowski, M. P. Thirugnanasambandam, L. Thomas, M. Thomas, P. Thomas, J. E. Thompson, S. R. Thondapu, K. A. Thorne, E. Thrane, Shubhanshu Tiwari, Srishti Tiwari, V. Tiwari, A. M. Toivonen, K. Toland, A. E. Tolley, T. Tomaru, Y. Tomigami, T. Tomura, M. Tonelli, A. Torres-Forné, C. I. Torrie, I. Tosta e Melo, D. Töyrä, A. Trapananti, F. Travasso, G. Traylor, M. Trevor, M. C. Tringali, A. Tripathee, L. Troiano, A. Trovato, L. Trozzo, R. J. Trudeau, D. S. Tsai, D. Tsai, K. W. Tsang, T. Tsang, J-S. Tsao, M. Tse, R. Tso, K. Tsubono, S. Tsuchida, L. Tsukada, D. Tsuna, T. Tsutsui, T. Tsuzuki, K. Turbang, M. Turconi, D. Tuyenbayev, A. S. Ubhi, N. Uchikata, T. Uchiyama, R. P. Udall, A. Ueda, T. Uehara, K. Ueno, G. Ueshima, C. S. Unnikrishnan, F. Uraguchi, A. L. Urban, T. Ushiba, A. Utina, H. Vahlbruch, G. Vajente, A. Vajpeyi, G. Valdes, M. Valentini, V. Valsan, N. van Bakel, M. van Beuzekom, J. F. J. van den Brand, C. Van Den Broeck, D. C. Vander-Hyde, L. van der Schaaf, J. V. van Heijningen, J. Vanosky, M. H. P. M. van Putten, N. van Remortel, M. Vardaro, A. F. Vargas, V. Varma, M. Vasúth, A. Vecchio, G. Vedovato, J. Veitch, P. J. Veitch, J. Venneberg, G. Venugopalan, D. Verkindt, P. Verma, Y. Verma, D. Veske, F. Vetrano, A. Viceré, S. Vidyant, A. D. Viets, A. Vijaykumar, V. Villa-Ortega, J.-Y. Vinet, A. Virtuoso, S. Vitale, T. Vo, H. Vocca, E. R. G. von Reis, J. S. A. von Wrangel, C. Vorvick, S. P. Vyatchanin, L. E. Wade, M. Wade, K. J. Wagner, R. C. Walet, M. Walker, G. S. Wallace, L. Wallace, S. Walsh, J. Wang, J. Z. Wang, W. H. Wang, R. L. Ward, J. Warner, M. Was, T. Washimi, N. Y. Washington, J. Watchi, B. Weaver, S. A. Webster, M. Weinert, A. J. Weinstein, R. Weiss, C. M. Weller, F. Wellmann, L. Wen, P. Weßels, K. Wette, J. T. Whelan, D. D. White, B. F. Whiting, C. Whittle, D. Wilken, D. Williams, M. J. Williams, A. R. Williamson, J. L. Willis, B. Willke, D. J. Wilson, W. Winkler, C. C. Wipf, T. Wlodarczyk, G. Woan, J. Woehler, J. K. Wofford, I. C. F. Wong, C. Wu, D. S. Wu, H. Wu, S. Wu, D. M. Wysocki, L. Xiao, W-R. Xu, T. Yamada, H. Yamamoto, Kazuhiro Yamamoto, Kohei Yamamoto, T. Yamamoto, K. Yamashita, R. Yamazaki, F. W. Yang, L. Yang, Y. Yang, Yang Yang, Z. Yang, M. J. Yap, D. W. Yeeles, A. B. Yelikar, M. Ying, K. Yokogawa, J. Yokoyama, T. Yokozawa, J. Yoo, T. Yoshioka, Hang Yu, Haocun Yu, H. Yuzurihara, A. Zadrożny, M. Zanolin, S. Zeidler, T. Zelenova, J.-P. Zendri, M. Zevin, M. Zhan, H. Zhang, J. Zhang, L. Zhang, T. Zhang, Y. Zhang, C. Zhao, G. Zhao, Y. Zhao, Yue Zhao, Y. Zheng, R. Zhou, Z. Zhou, X. J. Zhu, Z.-H. Zhu, A. B. Zimmerman, Y. Zlochower, M. E. Zucker, and J. Zweizig

Subjects
Physics, QC1-999
Abstract

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star–black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc^{−3} yr^{−1} and the neutron star–black hole merger rate to be between 7.8 and 140 Gpc^{−3} yr^{−1}, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc^{-3} yr^{-1} at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)^{κ} with κ=2.9_{-1.8}^{+1.7} for z≲1. Using both binary neutron star and neutron star–black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2_{-0.2}^{+0.1} to 2.0_{-0.3}^{+0.3}M_{⊙}. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3_{-0.5}^{+0.3} and 27.9_{-1.8}^{+1.9}M_{⊙}. While we continue to find that the mass distribution of a binary’s more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M_{⊙}, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χ_{i}≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum.

Published
2023
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43. Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Author

Timon Damelang, Elizabeth H. Aitken, Wina Hasang, Ester Lopez, Martin Killian, Holger W. Unger, Ali Salanti, Alexis Shub, Elizabeth McCarthy, Katherine Kedzierska, Martha Lappas, Stephen J. Kent, Stephen J. Rogerson, and Amy W. Chung

Subjects
Medicine, Science
Abstract

Abstract Immune effector responses against Plasmodium falciparum include antibody-mediated activation of innate immune cells, which can induce Fc effector functions, including antibody-dependent cellular cytotoxicity, and the secretion of cytokines and chemokines. These effector functions are regulated by the composition of immunoglobulin G (IgG) Fc N-linked glycans. However, a role for antibody-mediated natural killer (NK) cells activation or Fc N-linked glycans in pregnant women with malaria has not yet been established. Herein, we studied the capacity of IgG antibodies from pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3. Antibody-mediated NK cell activation was observed in pregnant women with malaria, but no differences were associated with susceptibility to placental malaria. Elevated anti-inflammatory glycosylation patterns of IgG antibodies were observed in pregnant women with or without malaria infection, which were not seen in healthy non-pregnant controls. This suggests that pregnancy-associated anti-inflammatory Fc N-linked glycans may dampen the antibody-mediated activation of NK cells in pregnant women with malaria infection. Overall, although anti-inflammatory glycans and antibody-dependent NK cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven.

Published
2021
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44. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Author

Adam K. Wheatley, Jennifer A. Juno, Jing J. Wang, Kevin J. Selva, Arnold Reynaldi, Hyon-Xhi Tan, Wen Shi Lee, Kathleen M. Wragg, Hannah G. Kelly, Robyn Esterbauer, Samantha K. Davis, Helen E. Kent, Francesca L. Mordant, Timothy E. Schlub, David L. Gordon, David S. Khoury, Kanta Subbarao, Deborah Cromer, Tom P. Gordon, Amy W. Chung, Miles P. Davenport, and Stephen J. Kent

Subjects
Science
Abstract

Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.

Published
2021
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45. Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

Author

Shidan Tosif, Melanie R. Neeland, Philip Sutton, Paul V. Licciardi, Sohinee Sarkar, Kevin J. Selva, Lien Anh Ha Do, Celeste Donato, Zheng Quan Toh, Rachel Higgins, Carolien Van de Sandt, Melissa M. Lemke, Christina Y. Lee, Suzanne K. Shoffner, Katie L. Flanagan, Kelly B. Arnold, Francesca L. Mordant, Kim Mulholland, Julie Bines, Kate Dohle, Daniel G. Pellicci, Nigel Curtis, Sarah McNab, Andrew Steer, Richard Saffery, Kanta Subbarao, Amy W. Chung, Katherine Kedzierska, David P. Burgner, and Nigel W. Crawford

Subjects
Science
Abstract

Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.

Published
2020
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46. A Quantitative Approach to Unravel the Role of Host Genetics in IgG-FcγR Complex Formation After Vaccination

Author

Melissa M. Lemke, Robert M. Theisen, Emily R. Bozich, Milla R. McLean, Christina Y. Lee, Ester Lopez, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Sven Kratochvil, Bruce D. Wines, P. Mark Hogarth, Stephen J. Kent, Amy W. Chung, and Kelly B. Arnold

Subjects
systems serology, Fc receptor, IgG1 allotype, Fc receptor polymorphism, HIV, RV144, Immunologic diseases. Allergy, RC581-607
Abstract

Fc-mediated immune functions have been correlated with protection in the RV144 HIV vaccine trial and are important for immunity to a range of pathogens. IgG antibodies (Abs) that form complexes with Fc receptors (FcRs) on innate immune cells can activate Fc-mediated immune functions. Genetic variation in both IgGs and FcRs have the capacity to alter IgG-FcR complex formation via changes in binding affinity and concentration. A growing challenge lies in unraveling the importance of multiple variations, especially in the context of vaccine trials that are conducted in homogenous genetic populations. Here we use an ordinary differential equation model to quantitatively assess how IgG1 allotypes and FcγR polymorphisms influence IgG-FcγRIIIa complex formation in vaccine-relevant settings. Using data from the RV144 HIV vaccine trial, we map the landscape of IgG-FcγRIIIa complex formation predicted post-vaccination for three different IgG1 allotypes and two different FcγRIIIa polymorphisms. Overall, the model illustrates how specific vaccine interventions could be applied to maximize IgG-FcγRIIIa complex formation in different genetic backgrounds. Individuals with the G1m1,17 and G1m1,3 allotypes were predicted to be more responsive to vaccine adjuvant strategies that increase antibody FcγRIIIa affinity (e.g. glycosylation modifications), compared to the G1m-1,3 allotype which was predicted to be more responsive to vaccine boosting regimens that increase IgG1 antibody titers (concentration). Finally, simulations in mixed-allotype populations suggest that the benefit of boosting IgG1 concentration versus IgG1 affinity may be dependent upon the presence of the G1m-1,3 allotype. Overall this work provides a quantitative tool for rationally improving Fc-mediated functions after vaccination that may be important for assessing vaccine trial results in the context of under-represented genetic populations.

Published
2022
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47. Heterologous SARS‐CoV‐2 IgA neutralising antibody responses in convalescent plasma

Author

Samantha K Davis, Kevin John Selva, Ester Lopez, Ebene R Haycroft, Wen Shi Lee, Adam K Wheatley, Jennifer A Juno, Amy Adair, Phillip Pymm, Samuel J Redmond, Nicholas A Gherardin, Dale I Godfrey, Wai‐Hong Tham, Stephen J Kent, and Amy W Chung

Subjects
ACE2 inhibition, Fc function, IgA, neutralisation, RBD, SARS‐CoV‐2, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Following infection with SARS‐CoV‐2, virus‐specific antibodies are generated, which can both neutralise virions and clear infection via Fc effector functions. The importance of IgG antibodies for protection and control of SARS‐CoV‐2 has been extensively reported. By comparison, other antibody isotypes including IgA have been poorly characterised. Methods Here, we characterised plasma IgA from 41 early convalescent COVID‐19 subjects for neutralisation and Fc effector functions. Results Convalescent plasma IgA from > 60% of the cohort had the capacity to inhibit the interaction between wild‐type RBD and ACE2. Furthermore, a third of the cohort induced stronger IgA‐mediated ACE2 inhibition than matched IgG when tested at equivalent concentrations. Plasma IgA and IgG from this cohort broadly recognised similar RBD epitopes and had similar capacities to inhibit ACE2 from binding to 22 of the 23 prevalent RBD mutations assessed. However, plasma IgA was largely incapable of mediating antibody‐dependent phagocytosis in comparison with plasma IgG. Conclusion Overall, convalescent plasma IgA contributed to the neutralising antibody response of wild‐type SARS‐CoV‐2 RBD and various RBD mutations. However, this response displayed large heterogeneity and was less potent than IgG.

Published
2022
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48. Search for Gravitational Waves Associated with Fast Radio Bursts Detected by CHIME/FRB during the LIGO–Virgo Observing Run O3a

Author

R. Abbott, T. D. Abbott, F. Acernese, K. Ackley, C. Adams, N. Adhikari, R. X. Adhikari, V. B. Adya, C. Affeldt, D. Agarwal, M. Agathos, K. Agatsuma, N. Aggarwal, O. D. Aguiar, L. Aiello, A. Ain, P. Ajith, T. Akutsu, S. Albanesi, A. Allocca, P. A. Altin, A. Amato, C. Anand, S. Anand, A. Ananyeva, S. B. Anderson, W. G. Anderson, M. Ando, T. Andrade, N. Andres, T. Andrić, S. V. Angelova, S. Ansoldi, J. M. Antelis, S. Antier, S. Appert, Koji Arai, Koya Arai, Y. Arai, S. Araki, A. Araya, M. C. Araya, J. S. Areeda, M. Arène, N. Aritomi, N. Arnaud, S. M. Aronson, K. G. Arun, H. Asada, Y. Asali, G. Ashton, Y. Aso, M. Assiduo, S. M. Aston, P. Astone, F. Aubin, C. Austin, S. Babak, F. Badaracco, M. K. M. Bader, C. Badger, S. Bae, Y. Bae, A. M. Baer, S. Bagnasco, Y. Bai, L. Baiotti, J. Baird, R. Bajpai, M. Ball, G. Ballardin, S. W. Ballmer, A. Balsamo, G. Baltus, S. Banagiri, D. Bankar, J. C. Barayoga, C. Barbieri, B. C. Barish, D. Barker, P. Barneo, F. Barone, B. Barr, L. Barsotti, M. Barsuglia, D. Barta, J. Bartlett, M. A. Barton, I. Bartos, R. Bassiri, A. Basti, M. Bawaj, J. C. Bayley, A. C. Baylor, M. Bazzan, B. Bécsy, V. M. Bedakihale, M. Bejger, I. Belahcene, V. Benedetto, D. Beniwal, T. F. Bennett, J. D. Bentley, M. BenYaala, F. Bergamin, B. K. Berger, S. Bernuzzi, C. P. L. Berry, D. Bersanetti, A. Bertolini, J. Betzwieser, D. Beveridge, R. Bhandare, U. Bhardwaj, D. Bhattacharjee, S. Bhaumik, I. A. Bilenko, G. Billingsley, S. Bini, I. A. Birney, O. Birnholtz, S. Biscans, M. Bischi, S. Biscoveanu, A. Bisht, B. Biswas, M. Bitossi, M.-A. Bizouard, J. K. Blackburn, C. D. Blair, D. G. Blair, R. M. Blair, F. Bobba, N. Bode, M. Boer, G. Bogaert, M. Boldrini, L. D. Bonavena, F. Bondu, E. Bonilla, R. Bonnand, P. Booker, B. A. Boom, R. Bork, V. Boschi, N. Bose, S. Bose, V. Bossilkov, V. Boudart, Y. Bouffanais, A. Boumerdassi, A. Bozzi, C. Bradaschia, P. R. Brady, A. Bramley, A. Branch, M. Branchesi, J. E. Brau, M. Breschi, T. Briant, J. H. Briggs, A. Brillet, M. Brinkmann, P. Brockill, A. F. Brooks, J. Brooks, D. D. Brown, S. Brunett, G. Bruno, R. Bruntz, J. Bryant, J. Buchanan, T. Bulik, H. J. Bulten, A. Buonanno, R. Buscicchio, D. Buskulic, C. Buy, R. L. Byer, L. Cadonati, G. Cagnoli, C. Cahillane, J. Calderón Bustillo, J. D. Callaghan, T. A. Callister, E. Calloni, J. Cameron, J. B. Camp, M. Canepa, S. Canevarolo, M. Cannavacciuolo, K. C. Cannon, H. Cao, Z. Cao, E. Capocasa, E. Capote, G. Carapella, F. Carbognani, J. B. Carlin, M. F. Carney, M. Carpinelli, G. Carrillo, G. Carullo, T. L. Carver, J. Casanueva Diaz, C. Casentini, G. Castaldi, S. Caudill, M. Cavaglià, F. Cavalier, R. Cavalieri, M. Ceasar, G. Cella, P. Cerdá-Durán, E. Cesarini, W. Chaibi, K. Chakravarti, S. Chalathadka Subrahmanya, E. Champion, C.-H. Chan, C. Chan, C. L. Chan, K. Chan, M. Chan, K. Chandra, P. Chanial, S. Chao, P. Charlton, E. A. Chase, E. Chassande-Mottin, C. Chatterjee, Debarati Chatterjee, Deep Chatterjee, M. Chaturvedi, S. Chaty, C. Chen, H. Y. Chen, J. Chen, K. Chen, X. Chen, Y.-B. Chen, Y.-R. Chen, Z. Chen, H. Cheng, C. K. Cheong, H. Y. Cheung, H. Y. Chia, F. Chiadini, C-Y. Chiang, G. Chiarini, R. Chierici, A. Chincarini, M. L. Chiofalo, A. Chiummo, G. Cho, H. S. Cho, R. K. Choudhary, S. Choudhary, N. Christensen, H. Chu, Q. Chu, Y-K. Chu, S. Chua, K. W. Chung, G. Ciani, P. Ciecielag, M. Cieślar, M. Cifaldi, A. A. Ciobanu, R. Ciolfi, F. Cipriano, A. Cirone, F. Clara, E. N. Clark, J. A. Clark, L. Clarke, P. Clearwater, S. Clesse, F. Cleva, E. Coccia, E. Codazzo, P.-F. Cohadon, D. E. Cohen, L. Cohen, M. Colleoni, C. G. Collette, A. Colombo, M. Colpi, C. M. Compton, M. Constancio Jr., L. Conti, S. J. Cooper, P. Corban, T. R. Corbitt, I. Cordero-Carrión, S. Corezzi, K. R. Corley, N. Cornish, D. Corre, A. Corsi, S. Cortese, C. A. Costa, R. Cotesta, M. W. Coughlin, J.-P. Coulon, S. T. Countryman, B. Cousins, P. Couvares, D. M. Coward, M. J. Cowart, D. C. Coyne, R. Coyne, J. D. E. Creighton, T. D. Creighton, A. W. Criswell, M. Croquette, S. G. Crowder, J. R. Cudell, T. J. Cullen, A. Cumming, R. Cummings, L. Cunningham, E. Cuoco, M. Curyło, P. Dabadie, T. Dal Canton, S. Dall’Osso, G. Dálya, A. Dana, L. M. DaneshgaranBajastani, B. D’Angelo, S. Danilishin, S. D’Antonio, K. Danzmann, C. Darsow-Fromm, A. Dasgupta, L. E. H. Datrier, S. Datta, V. Dattilo, I. Dave, M. Davier, G. S. Davies, D. Davis, M. C. Davis, E. J. Daw, R. Dean, D. DeBra, M. Deenadayalan, J. Degallaix, M. De Laurentis, S. Deléglise, V. Del Favero, F. De Lillo, N. De Lillo, W. Del Pozzo, L. M. DeMarchi, F. De Matteis, V. D’Emilio, N. Demos, T. Dent, A. Depasse, R. De Pietri, R. De Rosa, C. De Rossi, R. DeSalvo, R. De Simone, S. Dhurandhar, M. C. Díaz, M. Diaz-Ortiz Jr., N. A. Didio, T. Dietrich, L. Di Fiore, C. Di Fronzo, C. Di Giorgio, F. Di Giovanni, M. Di Giovanni, T. Di Girolamo, A. Di Lieto, B. Ding, S. Di Pace, I. Di Palma, F. Di Renzo, A. K. Divakarla, A. Dmitriev, Z. Doctor, L. D’Onofrio, F. Donovan, K. L. Dooley, S. Doravari, I. Dorrington, M. Drago, J. C. Driggers, Y. Drori, J.-G. Ducoin, P. Dupej, O. Durante, D. D’Urso, P.-A. Duverne, S. E. Dwyer, C. Eassa, P. J. Easter, M. Ebersold, T. Eckhardt, G. Eddolls, B. Edelman, T. B. Edo, O. Edy, A. Effler, S. Eguchi, J. Eichholz, S. S. Eikenberry, M. Eisenmann, R. A. Eisenstein, A. Ejlli, E. Engelby, Y. Enomoto, L. Errico, R. C. Essick, H. Estellés, D. Estevez, Z. Etienne, T. Etzel, M. Evans, T. M. Evans, B. E. Ewing, V. Fafone, H. Fair, S. Fairhurst, A. M. Farah, S. Farinon, B. Farr, W. M. Farr, N. W. Farrow, E. J. Fauchon-Jones, G. Favaro, M. Favata, M. Fays, M. Fazio, J. Feicht, M. M. Fejer, E. Fenyvesi, D. L. Ferguson, A. Fernandez-Galiana, I. Ferrante, T. A. Ferreira, F. Fidecaro, P. Figura, I. Fiori, M. Fishbach, R. P. Fisher, R. Fittipaldi, V. Fiumara, R. Flaminio, E. Floden, H. Fong, J. A. Font, B. Fornal, P. W. F. Forsyth, A. Franke, S. Frasca, F. Frasconi, C. Frederick, J. P. Freed, Z. Frei, A. Freise, R. Frey, P. Fritschel, V. V. Frolov, G. G. Fronzé, Y. Fujii, Y. Fujikawa, M. Fukunaga, M. Fukushima, P. Fulda, M. Fyffe, H. A. Gabbard, B. U. Gadre, J. R. Gair, J. Gais, S. Galaudage, R. Gamba, D. Ganapathy, A. Ganguly, D. Gao, S. G. Gaonkar, B. Garaventa, C. García-Núñez, C. García-Quirós, F. Garufi, B. Gateley, S. Gaudio, V. Gayathri, G.-G. Ge, G. Gemme, A. Gennai, J. George, O. Gerberding, L. Gergely, P. Gewecke, S. Ghonge, Abhirup Ghosh, Archisman Ghosh, Shaon Ghosh, Shrobana Ghosh, B. Giacomazzo, L. Giacoppo, J. A. Giaime, K. D. Giardina, D. R. Gibson, C. Gier, M. Giesler, P. Giri, F. Gissi, J. Glanzer, A. E. Gleckl, P. Godwin, E. Goetz, R. Goetz, N. Gohlke, B. Goncharov, G. González, A. Gopakumar, M. Gosselin, R. Gouaty, D. W. Gould, B. Grace, A. Grado, M. Granata, V. Granata, A. Grant, S. Gras, P. Grassia, C. Gray, R. Gray, G. Greco, A. C. Green, R. Green, A. M. Gretarsson, E. M. Gretarsson, D. Griffith, W. Griffiths, H. L. Griggs, G. Grignani, A. Grimaldi, S. J. Grimm, H. Grote, S. Grunewald, P. Gruning, D. Guerra, G. M. Guidi, A. R. Guimaraes, G. Guixé, H. K. Gulati, H.-K. Guo, Y. Guo, Anchal Gupta, Anuradha Gupta, P. Gupta, E. K. Gustafson, R. Gustafson, F. Guzman, S. Ha, L. Haegel, A. Hagiwara, S. Haino, O. Halim, E. D. Hall, E. Z. Hamilton, G. Hammond, W.-B. Han, M. Haney, J. Hanks, C. Hanna, M. D. Hannam, O. Hannuksela, H. Hansen, T. J. Hansen, J. Hanson, T. Harder, T. Hardwick, K. Haris, J. Harms, G. M. Harry, I. W. Harry, D. Hartwig, K. Hasegawa, B. Haskell, R. K. Hasskew, C.-J. Haster, K. Hattori, K. Haughian, H. Hayakawa, K. Hayama, F. J. Hayes, J. Healy, A. Heidmann, A. Heidt, M. C. Heintze, J. Heinze, J. Heinzel, H. Heitmann, F. Hellman, P. Hello, A. F. Helmling-Cornell, G. Hemming, M. Hendry, I. S. Heng, E. Hennes, J. Hennig, M. H. Hennig, A. G. Hernandez, F. Hernandez Vivanco, M. Heurs, S. Hild, P. Hill, Y. Himemoto, A. S. Hines, Y. Hiranuma, N. Hirata, E. Hirose, S. Hochheim, D. Hofman, J. N. Hohmann, D. G. Holcomb, N. A. Holland, I. J. Hollows, Z. J. Holmes, K. Holt, D. E. Holz, Z. Hong, P. Hopkins, J. Hough, S. Hourihane, E. J. Howell, C. G. Hoy, D. Hoyland, A. Hreibi, B-H. Hsieh, Y. Hsu, G-Z. Huang, H-Y. Huang, P. Huang, Y-C. Huang, Y.-J. Huang, Y. Huang, M. T. Hübner, A. D. Huddart, B. Hughey, D. C. Y. Hui, V. Hui, S. Husa, S. H. Huttner, R. Huxford, T. Huynh-Dinh, S. Ide, B. Idzkowski, A. Iess, B. Ikenoue, S. Imam, K. Inayoshi, C. Ingram, Y. Inoue, K. Ioka, M. Isi, K. Isleif, K. Ito, Y. Itoh, B. R. Iyer, K. Izumi, V. JaberianHamedan, T. Jacqmin, S. J. Jadhav, S. P. Jadhav, A. L. James, A. Z. Jan, K. Jani, J. Janquart, K. Janssens, N. N. Janthalur, P. Jaranowski, D. Jariwala, R. Jaume, A. C. Jenkins, K. Jenner, C. Jeon, M. Jeunon, W. Jia, H.-B. Jin, G. R. Johns, A. W. Jones, D. I. Jones, J. D. Jones, P. Jones, R. Jones, R. J. G. Jonker, L. Ju, P. Jung, K. Jung, J. Junker, V. Juste, K. Kaihotsu, T. Kajita, M. Kakizaki, C. V. Kalaghatgi, V. Kalogera, B. Kamai, M. Kamiizumi, N. Kanda, S. Kandhasamy, G. Kang, J. B. Kanner, Y. Kao, S. J. Kapadia, D. P. Kapasi, S. Karat, C. Karathanasis, S. Karki, R. Kashyap, M. Kasprzack, W. Kastaun, S. Katsanevas, E. Katsavounidis, W. Katzman, T. Kaur, K. Kawabe, K. Kawaguchi, N. Kawai, T. Kawasaki, F. Kéfélian, D. Keitel, J. S. Key, S. Khadka, F. Y. Khalili, S. Khan, E. A. Khazanov, N. Khetan, M. Khursheed, N. Kijbunchoo, C. Kim, J. C. Kim, J. Kim, K. Kim, W. S. Kim, Y.-M. Kim, C. Kimball, N. Kimura, M. Kinley-Hanlon, R. Kirchhoff, J. S. Kissel, N. Kita, H. Kitazawa, L. Kleybolte, S. Klimenko, A. M. Knee, T. D. Knowles, E. Knyazev, P. Koch, G. Koekoek, Y. Kojima, K. Kokeyama, S. Koley, P. Kolitsidou, M. Kolstein, K. Komori, V. Kondrashov, A. K. H. Kong, A. Kontos, N. Koper, M. Korobko, K. Kotake, M. Kovalam, D. B. Kozak, C. Kozakai, R. Kozu, V. Kringel, N. V. Krishnendu, A. Królak, G. Kuehn, F. Kuei, P. Kuijer, A. Kumar, P. Kumar, Rahul Kumar, Rakesh Kumar, J. Kume, K. Kuns, C. Kuo, H-S. Kuo, Y. Kuromiya, S. Kuroyanagi, K. Kusayanagi, S. Kuwahara, K. Kwak, P. Lagabbe, D. Laghi, E. Lalande, T. L. Lam, A. Lamberts, M. Landry, B. B. Lane, R. N. Lang, J. Lange, B. Lantz, I. La Rosa, A. Lartaux-Vollard, P. D. Lasky, M. Laxen, A. Lazzarini, C. Lazzaro, P. Leaci, S. Leavey, Y. K. Lecoeuche, H. K. Lee, H. M. Lee, H. W. Lee, J. Lee, K. Lee, R. Lee, J. Lehmann, A. Lemaître, M. Leonardi, N. Leroy, N. Letendre, C. Levesque, Y. Levin, J. N. Leviton, K. Leyde, A. K. Y. Li, B. Li, J. Li, K. L. Li, T. G. F. Li, X. Li, C-Y. Lin, F-K. Lin, F-L. Lin, H. L. Lin, L. C.-C. Lin, F. Linde, S. D. Linker, J. N. Linley, T. B. Littenberg, G. C. Liu, J. Liu, K. Liu, X. Liu, F. Llamas, M. Llorens-Monteagudo, R. K. L. Lo, A. Lockwood, L. T. London, A. Longo, D. Lopez, M. Lopez Portilla, M. Lorenzini, V. Loriette, M. Lormand, G. Losurdo, T. P. Lott, J. D. Lough, C. O. Lousto, G. Lovelace, J. F. Lucaccioni, H. Lück, D. Lumaca, A. P. Lundgren, L.-W. Luo, J. E. Lynam, R. Macas, M. MacInnis, D. M. Macleod, I. A. O. MacMillan, A. Macquet, I. Magaña Hernandez, C. Magazzù, R. M. Magee, R. Maggiore, M. Magnozzi, S. Mahesh, E. Majorana, C. Makarem, I. Maksimovic, S. Maliakal, A. Malik, N. Man, V. Mandic, V. Mangano, J. L. Mango, G. L. Mansell, M. Manske, M. Mantovani, M. Mapelli, F. Marchesoni, M. Marchio, F. Marion, Z. Mark, S. Márka, Z. Márka, C. Markakis, A. S. Markosyan, A. Markowitz, E. Maros, A. Marquina, S. Marsat, F. Martelli, I. W. Martin, R. M. Martin, M. Martinez, V. A. Martinez, V. Martinez, K. Martinovic, D. V. Martynov, E. J. Marx, H. Masalehdan, K. Mason, E. Massera, A. Masserot, T. J. Massinger, M. Masso-Reid, S. Mastrogiovanni, A. Matas, M. Mateu-Lucena, F. Matichard, M. Matiushechkina, N. Mavalvala, J. J. McCann, R. McCarthy, D. E. McClelland, P. K. McClincy, S. McCormick, L. McCuller, G. I. McGhee, S. C. McGuire, C. McIsaac, J. McIver, T. McRae, S. T. McWilliams, D. Meacher, M. Mehmet, A. K. Mehta, Q. Meijer, A. Melatos, D. A. Melchor, G. Mendell, A. Menendez-Vazquez, C. S. Menoni, R. A. Mercer, L. Mereni, K. Merfeld, E. L. Merilh, J. D. Merritt, M. Merzougui, S. Meshkov, C. Messenger, C. Messick, P. M. Meyers, F. Meylahn, A. Mhaske, A. Miani, H. Miao, I. Michaloliakos, C. Michel, Y. Michimura, H. Middleton, L. Milano, A. L. Miller, A. Miller, B. Miller, M. Millhouse, J. C. Mills, E. Milotti, O. Minazzoli, Y. Minenkov, N. Mio, Ll. M. Mir, M. Miravet-Tenés, C. Mishra, T. Mishra, T. Mistry, S. Mitra, V. P. Mitrofanov, G. Mitselmakher, R. Mittleman, O. Miyakawa, A. Miyamoto, Y. Miyazaki, K. Miyo, S. Miyoki, Geoffrey Mo, E. Moguel, K. Mogushi, S. R. P. Mohapatra, S. R. Mohite, I. Molina, M. Molina-Ruiz, M. Mondin, M. Montani, C. J. Moore, D. Moraru, F. Morawski, A. More, C. Moreno, G. Moreno, Y. Mori, S. Morisaki, Y. Moriwaki, B. Mours, C. M. Mow-Lowry, S. Mozzon, F. Muciaccia, Arunava Mukherjee, D. Mukherjee, Soma Mukherjee, Subroto Mukherjee, Suvodip Mukherjee, N. Mukund, A. Mullavey, J. Munch, E. A. Muñiz, P. G. Murray, R. Musenich, S. Muusse, S. L. Nadji, K. Nagano, S. Nagano, A. Nagar, K. Nakamura, H. Nakano, M. Nakano, R. Nakashima, Y. Nakayama, V. Napolano, I. Nardecchia, T. Narikawa, L. Naticchioni, B. Nayak, R. K. Nayak, R. Negishi, B. F. Neil, J. Neilson, G. Nelemans, T. J. N. Nelson, M. Nery, P. Neubauer, A. Neunzert, K. Y. Ng, S. W. S. Ng, C. Nguyen, P. Nguyen, T. Nguyen, L. Nguyen Quynh, W.-T. Ni, S. A. Nichols, A. Nishizawa, S. Nissanke, E. Nitoglia, F. Nocera, M. Norman, C. North, S. Nozaki, L. K. Nuttall, J. Oberling, B. D. O’Brien, Y. Obuchi, J. O’Dell, E. Oelker, W. Ogaki, G. Oganesyan, J. J. Oh, K. Oh, S. H. Oh, M. Ohashi, N. Ohishi, M. Ohkawa, F. Ohme, H. Ohta, M. A. Okada, Y. Okutani, K. Okutomi, C. Olivetto, K. Oohara, C. Ooi, R. Oram, B. O’Reilly, R. G. Ormiston, N. D. Ormsby, L. F. Ortega, R. O’Shaughnessy, E. O’Shea, S. Oshino, S. Ossokine, C. Osthelder, S. Otabe, D. J. Ottaway, H. Overmier, A. E. Pace, G. Pagano, M. A. Page, G. Pagliaroli, A. Pai, S. A. Pai, J. R. Palamos, O. Palashov, C. Palomba, H. Pan, K. Pan, P. K. Panda, H. Pang, P. T. H. Pang, C. Pankow, F. Pannarale, B. C. Pant, F. H. Panther, F. Paoletti, A. Paoli, A. Paolone, A. Parisi, H. Park, J. Park, W. Parker, D. Pascucci, A. Pasqualetti, R. Passaquieti, D. Passuello, M. Patel, M. Pathak, B. Patricelli, A. S. Patron, S. Patrone, S. Paul, E. Payne, M. Pedraza, M. Pegoraro, A. Pele, F. E. Peña Arellano, S. Penn, A. Perego, A. Pereira, T. Pereira, C. J. Perez, C. Périgois, C. C. Perkins, A. Perreca, S. Perriès, J. Petermann, D. Petterson, H. P. Pfeiffer, K. A. Pham, K. S. Phukon, O. J. Piccinni, M. Pichot, M. Piendibene, F. Piergiovanni, L. Pierini, V. Pierro, G. Pillant, M. Pillas, F. Pilo, L. Pinard, I. M. Pinto, M. Pinto, B. J. Piotrzkowski, K. Piotrzkowski, M. Pirello, M. D. Pitkin, E. Placidi, L. Planas, W. Plastino, C. Pluchar, R. Poggiani, E. Polini, D. Y. T. Pong, S. Ponrathnam, P. Popolizio, E. K. Porter, R. Poulton, J. Powell, M. Pracchia, T. Pradier, A. K. Prajapati, K. Prasai, R. Prasanna, G. Pratten, M. Principe, G. A. Prodi, L. Prokhorov, P. Prosposito, L. Prudenzi, A. Puecher, M. Punturo, F. Puosi, P. Puppo, M. Pürrer, H. Qi, V. Quetschke, R. Quitzow-James, F. J. Raab, G. Raaijmakers, H. Radkins, N. Radulesco, P. Raffai, S. X. Rail, S. Raja, C. Rajan, K. E. Ramirez, T. D. Ramirez, A. Ramos-Buades, J. Rana, P. Rapagnani, U. D. Rapol, A. Ray, V. Raymond, N. Raza, M. Razzano, J. Read, L. A. Rees, T. Regimbau, L. Rei, S. Reid, S. W. Reid, D. H. Reitze, P. Relton, A. Renzini, P. Rettegno, M. Rezac, F. Ricci, D. Richards, J. W. Richardson, L. Richardson, G. Riemenschneider, K. Riles, S. Rinaldi, K. Rink, M. Rizzo, N. A. Robertson, R. Robie, F. Robinet, A. Rocchi, S. Rodriguez, L. Rolland, J. G. Rollins, M. Romanelli, R. Romano, C. L. Romel, A. Romero-Rodríguez, I. M. Romero-Shaw, J. H. Romie, S. Ronchini, L. Rosa, C. A. Rose, D. Rosińska, M. P. Ross, S. Rowan, S. J. Rowlinson, S. Roy, Santosh Roy, Soumen Roy, D. Rozza, P. Ruggi, K. Ryan, S. Sachdev, T. Sadecki, J. Sadiq, N. Sago, S. Saito, Y. Saito, K. Sakai, Y. Sakai, M. Sakellariadou, Y. Sakuno, O. S. Salafia, L. Salconi, M. Saleem, F. Salemi, A. Samajdar, E. J. Sanchez, J. H. Sanchez, L. E. Sanchez, N. Sanchis-Gual, J. R. Sanders, A. Sanuy, T. R. Saravanan, N. Sarin, B. Sassolas, H. Satari, S. Sato, T. Sato, O. Sauter, R. L. Savage, T. Sawada, D. Sawant, H. L. Sawant, S. Sayah, D. Schaetzl, M. Scheel, J. Scheuer, M. Schiworski, P. Schmidt, S. Schmidt, R. Schnabel, M. Schneewind, R. M. S. Schofield, A. Schönbeck, B. W. Schulte, B. F. Schutz, E. Schwartz, J. Scott, S. M. Scott, M. Seglar-Arroyo, T. Sekiguchi, Y. Sekiguchi, D. Sellers, A. S. Sengupta, D. Sentenac, E. G. Seo, V. Sequino, A. Sergeev, Y. Setyawati, T. Shaffer, M. S. Shahriar, B. Shams, L. Shao, A. Sharma, P. Sharma, P. Shawhan, N. S. Shcheblanov, S. Shibagaki, M. Shikauchi, R. Shimizu, T. Shimoda, K. Shimode, H. Shinkai, T. Shishido, A. Shoda, D. H. Shoemaker, D. M. Shoemaker, S. ShyamSundar, M. Sieniawska, D. Sigg, L. P. Singer, D. Singh, N. Singh, A. Singha, A. M. Sintes, V. Sipala, V. Skliris, B. J. J. Slagmolen, T. J. Slaven-Blair, J. Smetana, J. R. Smith, R. J. E. Smith, J. Soldateschi, S. N. Somala, K. Somiya, E. J. Son, K. Soni, S. Soni, V. Sordini, F. Sorrentino, N. Sorrentino, H. Sotani, R. Soulard, T. Souradeep, E. Sowell, V. Spagnuolo, A. P. Spencer, M. Spera, R. Srinivasan, A. K. Srivastava, V. Srivastava, K. Staats, C. Stachie, D. A. Steer, J. Steinlechner, S. Steinlechner, D. J. Stops, M. Stover, K. A. Strain, L. C. Strang, G. Stratta, A. Strunk, R. Sturani, A. L. Stuver, S. Sudhagar, V. Sudhir, R. Sugimoto, H. G. Suh, T. Z. Summerscales, H. Sun, L. Sun, S. Sunil, A. Sur, J. Suresh, P. J. Sutton, Takamasa Suzuki, Toshikazu Suzuki, B. L. Swinkels, M. J. Szczepańczyk, P. Szewczyk, M. Tacca, H. Tagoshi, S. C. Tait, H. Takahashi, R. Takahashi, A. Takamori, S. Takano, H. Takeda, M. Takeda, C. J. Talbot, C. Talbot, H. Tanaka, Kazuyuki Tanaka, Kenta Tanaka, Taiki Tanaka, Takahiro Tanaka, A. J. Tanasijczuk, S. Tanioka, D. B. Tanner, D. Tao, L. Tao, E. N. Tapia San Martin, E. N. Tapia San Martín, C. Taranto, J. D. Tasson, S. Telada, R. Tenorio, J. E. Terhune, L. Terkowski, M. P. Thirugnanasambandam, M. Thomas, P. Thomas, J. E. Thompson, S. R. Thondapu, K. A. Thorne, E. Thrane, Shubhanshu Tiwari, Srishti Tiwari, V. Tiwari, A. M. Toivonen, K. Toland, A. E. Tolley, T. Tomaru, Y. Tomigami, T. Tomura, M. Tonelli, A. Torres-Forné, C. I. Torrie, I. Tosta e Melo, D. Töyrä, A. Trapananti, F. Travasso, G. Traylor, M. Trevor, M. C. Tringali, A. Tripathee, L. Troiano, A. Trovato, L. Trozzo, R. J. Trudeau, D. S. Tsai, D. Tsai, K. W. Tsang, T. Tsang, J-S. Tsao, M. Tse, R. Tso, K. Tsubono, S. Tsuchida, L. Tsukada, D. Tsuna, T. Tsutsui, T. Tsuzuki, K. Turbang, M. Turconi, D. Tuyenbayev, A. S. Ubhi, N. Uchikata, T. Uchiyama, R. P. Udall, A. Ueda, T. Uehara, K. Ueno, G. Ueshima, C. S. Unnikrishnan, F. Uraguchi, A. L. Urban, T. Ushiba, A. Utina, H. Vahlbruch, G. Vajente, A. Vajpeyi, G. Valdes, M. Valentini, V. Valsan, N. van Bakel, M. van Beuzekom, J. F. J. van den Brand, C. Van Den Broeck, D. C. Vander-Hyde, L. van der Schaaf, J. V. van Heijningen, J. Vanosky, M. H. P. M. van Putten, N. van Remortel, M. Vardaro, A. F. Vargas, V. Varma, M. Vasúth, A. Vecchio, G. Vedovato, J. Veitch, P. J. Veitch, J. Venneberg, G. Venugopalan, D. Verkindt, P. Verma, Y. Verma, D. Veske, F. Vetrano, A. Viceré, S. Vidyant, A. D. Viets, A. Vijaykumar, V. Villa-Ortega, J.-Y. Vinet, A. Virtuoso, S. Vitale, T. Vo, H. Vocca, E. R. G. von Reis, J. S. A. von Wrangel, C. Vorvick, S. P. Vyatchanin, L. E. Wade, M. Wade, K. J. Wagner, R. C. Walet, M. Walker, G. S. Wallace, L. Wallace, S. Walsh, J. Wang, J. Z. Wang, W. H. Wang, R. L. Ward, J. Warner, M. Was, T. Washimi, N. Y. Washington, K. Watada, J. Watchi, B. Weaver, S. A. Webster, M. Weinert, A. J. Weinstein, R. Weiss, C. M. Weller, F. Wellmann, L. Wen, P. Weßels, K. Wette, J. T. Whelan, D. D. White, B. F. Whiting, C. Whittle, D. Wilken, D. Williams, M. J. Williams, A. R. Williamson, J. L. Willis, B. Willke, D. J. Wilson, W. Winkler, C. C. Wipf, T. Wlodarczyk, G. Woan, J. Woehler, J. K. Wofford, I. C. F. Wong, C. Wu, D. S. Wu, H. Wu, S. Wu, D. M. Wysocki, L. Xiao, W-R. Xu, T. Yamada, H. Yamamoto, Kazuhiro Yamamoto, Kohei Yamamoto, T. Yamamoto, K. Yamashita, R. Yamazaki, F. W. Yang, L. Yang, Y. Yang, Yang Yang, Z. Yang, M. J. Yap, D. W. Yeeles, A. B. Yelikar, M. Ying, K. Yokogawa, J. Yokoyama, T. Yokozawa, J. Yoo, T. Yoshioka, Hang Yu, Haocun Yu, H. Yuzurihara, A. Zadrożny, M. Zanolin, S. Zeidler, T. Zelenova, J.-P. Zendri, M. Zevin, M. Zhan, H. Zhang, J. Zhang, L. Zhang, T. Zhang, Y. Zhang, C. Zhao, G. Zhao, Y. Zhao, Yue Zhao, R. Zhou, Z. Zhou, X. J. Zhu, Z.-H. Zhu, A. B. Zimmerman, M. E. Zucker, J. Zweizig, M. Bhardwaj, P. J. Boyle, T. Cassanelli, F. Dong, E. Fonseca, V. Kaspi, C. Leung, K. W. Masui, B. W. Meyers, D. Michilli, C. Ng, A. B. Pearlman, E. Petroff, Z. Pleunis, M. Rafiei-Ravandi, M. Rahman, S. Ransom, P. Scholz, K. Shin, K. Smith, I. Stairs, S. P. Tendulkar, A. V. Zwaniga, The LIGO Scientific Collaboration, The Virgo Collaboration, The KAGRA Collaboration, and The CHIME/FRB Collaboration

Subjects
Gravitational wave astronomy, Radio transient sources, Astrophysics, QB460-466
Abstract

We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 10 ^51 –10 ^57 erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB.

Published
2023
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49. Cross-reactive antibodies after SARS-CoV-2 infection and vaccination

Author

Marloes Grobben, Karlijn van der Straten, Philip JM Brouwer, Mitch Brinkkemper, Pauline Maisonnasse, Nathalie Dereuddre-Bosquet, Brent Appelman, AH Ayesha Lavell, Lonneke A van Vught, Judith A Burger, Meliawati Poniman, Melissa Oomen, Dirk Eggink, Tom PL Bijl, Hugo DG van Willigen, Elke Wynberg, Bas J Verkaik, Orlane JA Figaroa, Peter J de Vries, Tessel M Boertien, Amsterdam UMC COVID-19 S3/HCW study group, Marije K Bomers, Jonne J Sikkens, Roger Le Grand, Menno D de Jong, Maria Prins, Amy W Chung, Godelieve J de Bree, Rogier W Sanders, and Marit J van Gils

Subjects
antibodies, SARS-CoV-2, coronavirus, cross-reactivity, vaccine, COVID-19, Medicine, Science, Biology (General), QH301-705.5
Abstract

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

Published
2021
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50. Successful Liver Transplantation in a Patient With Acute COVID-19 Infection and Acute Liver Failure: A Case Report

Author

Kristen M. Kidson, MD, FRCPC, Jeieung Park, MD, FRCPC, Marthe K. Charles, MD, MSc, FRCPC, Mahmoud Omar, MD, MSc, Mel Krajden, MD, FRCPC, Alissa J. Wright, MD, MSc, FRCPC, Trana Hussaini, PharmD, Peter T. W. Kim, MD, MSc, FRCSC, Stephen W. Chung, MD, PhD, FRCSC, and Eric M. Yoshida, MD, MHSc, FRCPC

Subjects
Surgery, RD1-811
Abstract

Current liver transplantation societies recommend recipients with active coronavirus disease 2019 (COVID-19) be deferred from transplantation for at least 2 wks, have symptom resolution and at least 1 negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test.1 This approach does not address patients who require urgent transplantation and will otherwise die from liver failure. We report a successful orthotopic liver transplant (OLT) in a patient with active COVID-19 infection. This is only the second to be reported worldwide and the first in Canada.

Published
2021
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