7 results on '"Holly L. Hammond"'
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2. Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine
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Prabhu S. Arunachalam, Yupeng Feng, Usama Ashraf, Mengyun Hu, Alexandra C. Walls, Venkata Viswanadh Edara, Veronika I. Zarnitsyna, Pyone Pyone Aye, Nadia Golden, Marcos C. Miranda, Kristyn W. M. Green, Breanna M. Threeton, Nicholas J. Maness, Brandon J. Beddingfield, Rudolf P. Bohm, Sarah E. Scheuermann, Kelly Goff, Jason Dufour, Kasi Russell-Lodrigue, Elizabeth Kepl, Brooke Fiala, Samuel Wrenn, Rashmi Ravichandran, Daniel Ellis, Lauren Carter, Kenneth Rogers, Lisa M. Shirreff, Douglas E. Ferrell, Nihar R. Deb Adhikary, Jane Fontenot, Holly L. Hammond, Matthew Frieman, Alba Grifoni, Alessandro Sette, Derek T. O’Hagan, Robbert Van Der Most, Rino Rappuoli, Francois Villinger, Harry Kleanthous, Jay Rappaport, Mehul S. Suthar, David Veesler, Taia T. Wang, Neil P. King, and Bali Pulendran
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COVID-19 Vaccines ,Adjuvants, Immunologic ,SARS-CoV-2 ,Vaccines, Subunit ,Animals ,COVID-19 ,Humans ,Viral Vaccines ,General Medicine ,Antibodies, Viral ,Antibodies, Neutralizing - Abstract
Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.
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- 2022
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3. Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial
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Raburn M Mallory, Neil Formica, Susan Pfeiffer, Bethanie Wilkinson, Alex Marcheschi, Gary Albert, Heather McFall, Michelle Robinson, Joyce S Plested, Mingzhu Zhu, Shane Cloney-Clark, Bin Zhou, Gordon Chau, Andreana Robertson, Sonia Maciejewski, Holly L Hammond, Lauren Baracco, James Logue, Matthew B Frieman, Gale Smith, Nita Patel, Gregory M Glenn, Mark Adams, Mark Arya, Eugene Athan, Ira Berger, Paul Bradley, Toby Briskin, Richard Glover II, Paul Griffin, Joshua Kim, Scott Kitchener, Terry Klein, Amber Leah, Indika Leelasena, Charlotte Lemech, Jason Lickliter, Mary Beth Manning, Fiona Napier-Flood, Paul Nugent, Susan Thackwray, and Mark Turner
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Adult ,Vaccines ,COVID-19 Vaccines ,SARS-CoV-2 ,COVID-19 ,Antibodies, Viral ,Infectious Diseases ,Immunogenicity, Vaccine ,Adjuvants, Immunologic ,Double-Blind Method ,Spike Glycoprotein, Coronavirus ,Humans ,Female ,Pandemics - Abstract
Emerging SARS-CoV-2 variants and evidence of waning vaccine efficacy present substantial obstacles towards controlling the COVID-19 pandemic. Booster doses of SARS-CoV-2 vaccines might address these concerns by amplifying and broadening the immune responses seen with initial vaccination regimens. We aimed to assess the immunogenicity and safety of a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373).This secondary analysis of a phase 2, randomised study assessed a single booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) in healthy adults aged 18-84 years, recruited from 17 clinical centres in the USA and Australia. Eligible participants had a BMI of 17-35 kg/msup2/supand, for women, were heterosexually inactive or using contraception. Participants who had a history of SARS-CoV or SARS-CoV-2, confirmed diagnosis of COVID-19, serious chronic medical conditions, or were pregnant or breastfeeding were excluded. Approximately 6 months following their primary two-dose vaccination series (administered day 0 and day 21), participants who received placebo for their primary vaccination series received a placebo booster (group A) and participants who received NVX-CoV2373 for their primary vaccination series (group B) were randomly assigned (1:1) again, via centralised interactive response technology system, to receive either placebo (group B1) or a single booster dose of NVX-CoV2373 (5 μg SARS-CoV-2 rS with 50 μg Matrix-M adjuvant; group B2) via intramuscular injection; randomisation was stratified by age and study site. Vaccinations were administered by designated site personnel who were masked to treatment assignment, and participants and other site staff were also masked. Administration personnel also assessed the outcome. The primary endpoints are safety (unsolicited adverse events) and reactogenicity (solicited local and systemic) events and immunogenicity (serum IgG antibody concentrations for the SARS-CoV-2 rS protein antigen) assessed 14 days after the primary vaccination series (day 35) and 28 days following booster (day 217). Safety was analysed in all participants in groups A, B1, and B2, according to the treatment received; immunogenicity was analysed in the per-protocol population (ie, participants in groups A, B1, and B2) who received all assigned doses and who did not test SARS-CoV-2-positive or received an authorised vaccine, analysed according to treatment assignment). This trial is registered with ClinicalTrials.gov, NCT04368988.1610 participants were screened from Aug 24, 2020, to Sept 25, 2020. 1282 participants were enrolled, of whom 173 were assigned again to placebo (group A), 106 were re-randomised to NVX-CoV2373-placebo (group B1), and 104 were re-randomised to NVX-CoV2373-NVX-CoV2373 (group B2); after accounting for exclusions and incorrect administration, 172 participants in group A, 102 in group B1, and 105 in group B2 were analysed for safety. Following the active booster, the proportion of participants with available data reporting local (80 [82%] of 97 participants had any adverse event; 13 [13%] had a grade ≥3 event) and systemic (75 [77%] of 98 participants had any adverse event; 15 [15%] had a grade ≥3 event) reactions was higher than after primary vaccination (175 [70%] of 250 participants had any local adverse event, 13 [5%] had a grade ≥3 event; 132 [53%] of 250 had any systemic adverse event, 14 [6%] had a grade ≥3 event). Local and systemic events were transient in nature (median duration 1·0-2·5 days). In the per-protocol immunogenicity population at day 217 (167 participants in group A, 101 participants in group B1, 101 participants in group B2), IgG geometric mean titres (GMT) had increased by 4·7-fold and MNsub50/subGMT by 4·1-fold for the ancestral SARS-CoV-2 strain compared with the day 35 titres.Administration of a booster dose of NVX-CoV2373 resulted in an incremental increase in reactogenicity. For both the prototype strain and all variants evaluated, immune responses following the booster were similar to or higher than those associated with high levels of efficacy in phase 3 studies of the vaccine. These data support the use of NVX-CoV2373 in booster programmes.Novavax and the Coalition for Epidemic Preparedness Innovations.
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- 2022
4. Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection
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Jason F. Huntley, Lloyd S. Miller, Preeti Shahi, Michail Kotsyfakis, Adela S. Oliva Chávez, Eileen M. Barry, Laura Santambrogio, Daniel E. Sonenshine, Choukri Ben Mamoun, Holly L. Hammond, Steven M. Jay, Shelby L Ford, L. Rainer Butler, Kateryna Morozova, Utpal Pal, Brandi E. Hobbs, Dana K. Shaw, Glen A. Scoles, Joao H. F. Pedra, Xiaowei Wang, Amanda D. Buskirk, Cristina C. Clement, Brenden G. Tully, Jesus G. Valenzuela, Liron Marnin, Nathan K. Archer, Michael Levin, Anya J.O’ Neal, Marcela F. Pasetti, Erin E.Mc Clure Carroll, Kathleen L. Mason, Marcelo B. Sztein, and Lauren Lawres
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Male ,Proteomics ,0301 basic medicine ,Intravital Microscopy ,Vesicle-Associated Membrane Protein 2 ,T-Lymphocytes ,General Physics and Astronomy ,R-SNARE Proteins ,Mice ,Ticks ,Tandem Mass Spectrometry ,Francisella tularensis ,Pathogen ,Skin ,Mice, Knockout ,Multidisciplinary ,biology ,Bacterial Infections ,Ixodes scapularis ,Infectious diseases ,Pathogens ,Anaplasma phagocytophilum ,Science ,030106 microbiology ,Tick ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Microbiology ,Extracellular Vesicles ,03 medical and health sciences ,Microscopy, Electron, Transmission ,parasitic diseases ,Animals ,Humans ,Skin immunity ,Dermacentor andersoni ,Arthropods ,Dermacentor ,Inflammation ,Ixodes ,Bacteria ,General Chemistry ,bacterial infections and mycoses ,biology.organism_classification ,Mice, Inbred C57BL ,Gene Ontology ,030104 developmental biology ,Vector (epidemiology) ,Entomology - Abstract
Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases., Extracellular vesicles have been implicated in the transmission of pathogens from the arthropod to the human host. Here the authors show that tick-derived extracellular vesicles play a role in feeding and modulate the outcome of bacterial infection.
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- 2021
5. Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity
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Etsuro Nanishi, Francesco Borriello, Timothy R. O’Meara, Marisa E. McGrath, Yoshine Saito, Robert E. Haupt, Hyuk-Soo Seo, Simon D. van Haren, Byron Brook, Jing Chen, Joann Diray-Arce, Simon Doss-Gollin, Maria De Leon, Katherine Chew, Manisha Menon, Kijun Song, Andrew Z. Xu, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Amy C. Sherman, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Stuart M. Weston, Robert M. Johnson, Holly L. Hammond, Romana Mayer, Allen Burke, Maria E. Bottazzi, Peter J. Hotez, Ulrich Strych, Aiquan Chang, Jingyou Yu, Dan H. Barouch, Sirano Dhe-Paganon, Ivan Zanoni, Al Ozonoff, Matthew B. Frieman, Ofer Levy, and David J. Dowling
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Chemokine ,COVID-19 Vaccines ,CpG Oligodeoxynucleotide ,Aluminum Hydroxide ,Context (language use) ,Antibodies, Viral ,Article ,Mice ,Animals ,Humans ,Medicine ,Pandemics ,BNT162 Vaccine ,Aged ,Vaccines, Synthetic ,biology ,SARS-CoV-2 ,business.industry ,Immunogenicity ,COVID-19 ,TLR9 ,Antibodies, Neutralizing ,CpG site ,Spike Glycoprotein, Coronavirus ,Immunology ,TLR3 ,biology.protein ,mRNA Vaccines ,Antibody ,business - Abstract
Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need. Receptor-binding domain (RBD) is a key target of neutralizing antibodies (Abs) but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists, including those activating STING, TLR3, TLR4 and TLR9, alone or formulated with aluminum hydroxide (AH), and benchmarked them to AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that the AH and CpG adjuvant formulation (AH:CpG) demonstrated the highest enhancement of anti-RBD neutralizing Ab titers in both age groups (∼80-fold over AH), and protected aged mice from the SARS-CoV-2 challenge. Notably, AH:CpG-adjuvanted RBD vaccine elicited neutralizing Abs against both wild-type SARS-CoV-2 and B.1.351 variant at serum concentrations comparable to those induced by the authorized mRNA BNT162b2 vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and synergistically enhanced cytokine and chemokine production in human young adult and elderly mononuclear cells. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.One Sentence SummaryAlum and CpG enhance SARS-CoV-2 RBD protective immunity, variant neutralization in aged mice and Th1-polarizing cytokine production by human elder leukocytes.
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- 2021
6. Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19
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Heather Eng, Annaliesa S. Anderson, Norimitsu Shirai, Brandon J. Anson, James Logue, Stuart Weston, Marisa McGrath, Martyn D. Ticehurst, Rebecca E. O’Connor, Michelle Rossulek, Martin Pettersson, Matthew N O' Brien, Jean G. Sathish, Matthew B. Frieman, Emi Kimoto, Jun Wang, R. Scott Obach, Emily I. Chen, Robert Haupt, Yuao Zhu, Thomas F. Rogers, Andrew D. Mesecar, Suman Luthra, Adolfo García-Sastre, Dafydd R. Owen, Rhys M. Jones, Eugene P. Kadar, Chunlong Ma, Rob Kania, Lisa Aschenbrenner, Arnab K. Chatterjee, Charlotte Moira Norfor Allerton, Joseph John Binder, Kevin Ogilvie, Holly L. Hammond, Nathan Beutler, Claire M. Steppan, Jennifer Hammond, Stephen Noell, Romel Rosales, Robert M. Hoffman, Lillis Jonathan Richard, Matthew R. Reese, Stephen W. Mason, Dan Arenson, Malina A. Bakowski, Lawrence W. Updyke, Lorraine F. Lanyon, Kris M. White, Emma K. Lendy, Melanie G. Kirkpatrick, and Britton Boras
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Indoles ,Science ,medicine.medical_treatment ,viruses ,General Physics and Astronomy ,Pharmacology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Article ,Mice ,In vivo ,Coronavirus 229E, Human ,Leucine ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Protease inhibitor (pharmacology) ,skin and connective tissue diseases ,Infusions, Intravenous ,Vero Cells ,Coronavirus 3C Proteases ,Coronavirus ,ADME ,Multidisciplinary ,Protease ,Alanine ,Chemistry ,SARS-CoV-2 ,fungi ,COVID-19 ,Drug Synergism ,General Chemistry ,Prodrug ,In vitro ,Adenosine Monophosphate ,Pyrrolidinones ,respiratory tract diseases ,COVID-19 Drug Treatment ,body regions ,Disease Models, Animal ,Coronavirus Protease Inhibitors ,Severe acute respiratory syndrome-related coronavirus ,Drug Design ,Drug Therapy, Combination ,HeLa Cells - Abstract
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
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- 2021
7. Infection-derived lipids elicit an immune deficiency circuit in arthropods
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Alison J. Scott, Alexis A. Smith, Lei Liu, Holly L. Hammond, Massaro W. Ueti, Eric J. Sundberg, Robert K. Ernst, Joao H. F. Pedra, Greg A. Snyder, Dana K. Shaw, Margarita Villar, Vishant Mahendra Boradia, Xiaowei Wang, Kathryn E. Reif, Adela S. Oliva Chávez, Erin E. McClure, José de la Fuente, Utpal Pal, Erol Fikrig, Kathleen DePonte, Lindsey J. Brown, National Institute of Allergy and Infectious Diseases (US), University of Maryland, and National Institutes of Health (US)
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0301 basic medicine ,Fas-Associated Death Domain Protein ,General Physics and Astronomy ,Drosophila Proteins ,FADD ,RNA, Small Interfering ,Lyme Disease ,Multidisciplinary ,biology ,Pattern recognition receptor ,Signal transducing adaptor protein ,Phosphatidylglycerols ,Lipids ,Transmembrane protein ,Recombinant Proteins ,3. Good health ,Ubiquitin ligase ,Cell biology ,Anaplasma marginale ,Drosophila melanogaster ,lipids (amino acids, peptides, and proteins) ,Anaplasma phagocytophilum ,Signal Transduction ,Ubiquitin-Protein Ligases ,Science ,030106 microbiology ,X-Linked Inhibitor of Apoptosis Protein ,Inhibitor of apoptosis ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,parasitic diseases ,Escherichia coli ,Animals ,Humans ,Gene Silencing ,Borrelia burgdorferi ,Arthropods ,Diacylglycerol kinase ,Adaptor Proteins, Signal Transducing ,Ixodes ,Immunologic Deficiency Syndromes ,General Chemistry ,biology.organism_classification ,bacterial infections and mycoses ,Disease Models, Animal ,030104 developmental biology ,HEK293 Cells ,Ubiquitin-Conjugating Enzymes ,biology.protein ,Carrier Proteins ,Transcription Factors - Abstract
The insect immune deficiency (IMD) pathway resembles the tumour necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties activate the IMD signalling cascade remains unknown. Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks. The tick IMD network protects against colonization by three distinct bacteria, that is the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale. Cell signalling ensues in the absence of transmembrane peptidoglycan recognition proteins and the adaptor molecules Fas-associated protein with a death domain (FADD) and IMD. Conversely, biochemical interactions occur between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme Bendless. We propose the existence of two functionally distinct IMD networks, one in insects and another in ticks., This work was supported by the National Institutes of Health (R01 AI093653 and R01AI116523 to J.H.F.P.) and the University of Maryland, Baltimore School of Medicine. E.E.M. was a trainee under the Institutional Training Grant T32AI007540 from the National Institute of Allergy and Infectious Diseases.
- Published
- 2017
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