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1. Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption

Author

Pereira Ribeiro, Susan, Strongin, Zachary, Soudeyns, Hugo, ten-Caten, Felipe, Ghneim, Khader, Pacheco Sanchez, Gabriela, Xavier de Medeiros, Giuliana, Del Rio Estrada, Perla Mariana, Pelletier, Adam-Nicolas, Hoang, Timothy, Nguyen, Kevin, Harper, Justin, Jean, Sherrie, Wallace, Chelsea, Balderas, Robert, Lifson, Jeffrey D., Raghunathan, Gopalan, Rimmer, Eric, Pastuskova, Cinthia, Wu, Guoxin, Micci, Luca, Ribeiro, Ruy M., Chan, Chi Ngai, Estes, Jacob D., Silvestri, Guido, Gorman, Daniel M., Howell, Bonnie J., Hazuda, Daria J., Paiardini, Mirko, and Sekaly, Rafick P.

Published
2024
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2. Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVAD8-EO infection

Author

Dias, Joana, Fabozzi, Giulia, Fourati, Slim, Chen, Xuejun, Liu, Cuiping, Ambrozak, David R., Ransier, Amy, Laboune, Farida, Hu, Jianfei, Shi, Wei, March, Kylie, Maximova, Anna A., Schmidt, Stephen D., Samsel, Jakob, Talana, Chloe A., Ernste, Keenan, Ko, Sung Hee, Lucas, Margaret E., Radecki, Pierce E., Boswell, Kristin L., Nishimura, Yoshiaki, Todd, John-Paul, Martin, Malcolm A., Petrovas, Constantinos, Boritz, Eli A., Doria-Rose, Nicole A., Douek, Daniel C., Sékaly, Rafick-Pierre, Lifson, Jeffrey D., Asokan, Mangaiarkarasi, Gama, Lucio, Mascola, John R., Pegu, Amarendra, and Koup, Richard A.

Published
2024
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4. Embedding Internal Accountability Into Health Care Institutions for Safe, Effective, and Ethical Implementation of Artificial Intelligence Into Medical Practice: A Mayo Clinic Case Study

Author

Brenna Loufek, MS, David Vidal, JD, David S. McClintock, MD, Mark Lifson, PhD, Eric Williamson, MD, Shauna Overgaard, PhD, Kathleen McNaughton, JD, Melissa C. Lipford, MD, and Darrell S. Pardi, MD

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Health care organizations are building, deploying, and self-governing digital health technologies (DHTs), including artificial intelligence, at an increasing rate. This scope necessitates expertise and quality infrastructure to ensure that the technology impacting patient care is safe, effective, and ethical throughout its lifecycle. The objective of this article is to describe Mayo Clinic’s approach for embedding internal accountability as a case study for other health care institutions seeking modalities for responsible implementation of artificial intelligence–enabled DHTs. Mayo Clinic aims to enable and empower innovators by (1) building internal skills and expertise, (2) establishing a centralized review board, and (3) aligning development and deployment processes with regulations, standards, and best practices. In 2022, Mayo Clinic established the Software as a Medical Device Review Board (The Board), an independent body of physicians and domain experts to represent the organization in providing innovators regulatory and risk mitigation recommendations for DHTs. Hundreds of digital health product teams have since benefited from this function, intended to enable responsible innovation in alignment with regulation and state-of-the-art quality management practices. Other health care institutions can adopt similar internal accountability bodies using this framework. Opportunity remains to iterate on Mayo Clinic’s approach in alignment with advancing best practices and enhance representation on The Board as part of standard continuous improvement practices.

Published
2024
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5. Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVAD8-EO infection

Author

Joana Dias, Giulia Fabozzi, Slim Fourati, Xuejun Chen, Cuiping Liu, David R. Ambrozak, Amy Ransier, Farida Laboune, Jianfei Hu, Wei Shi, Kylie March, Anna A. Maximova, Stephen D. Schmidt, Jakob Samsel, Chloe A. Talana, Keenan Ernste, Sung Hee Ko, Margaret E. Lucas, Pierce E. Radecki, Kristin L. Boswell, Yoshiaki Nishimura, John-Paul Todd, Malcolm A. Martin, Constantinos Petrovas, Eli A. Boritz, Nicole A. Doria-Rose, Daniel C. Douek, Rafick-Pierre Sékaly, Jeffrey D. Lifson, Mangaiarkarasi Asokan, Lucio Gama, John R. Mascola, Amarendra Pegu, and Richard A. Koup

Subjects
Science
Abstract

Abstract Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIVAD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8+ CD69+ T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.

Published
2024
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6. Acute-phase innate immune responses in SIVmac239-infected Mamu-B*08+ Indian rhesus macaques may contribute to the establishment of elite control

Author

Brandon C. Rosen, Kaitlin Sawatzki, Michael J. Ricciardi, Elise Smith, Inah Golez, Jack T. Mauter, Núria Pedreño-López, Aaron Yrizarry-Medina, Kim L. Weisgrau, Logan J. Vosler, Thomas B. Voigt, Johan J. Louw, Jennifer Tisoncik-Go, Leanne S. Whitmore, Christakis Panayiotou, Noor Ghosh, Jessica R. Furlott, Christopher L. Parks, Ronald C. Desrosiers, Jeffrey D. Lifson, Eva G. Rakasz, David I. Watkins, and Michael Gale

Subjects
simian immunodeficiency virus (SIV), cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV), vaccines, acquired immunodeficiency syndrome (AIDS), Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionSpontaneous control of chronic-phase HIV/SIV viremia is often associated with the expression of specific MHC class I allotypes. HIV/SIV-specific CD8+ cytotoxic T lymphocytes (CTLs) restricted by these MHC class I allotypes appear to be critical for viremic control. Establishment of the elite controller (EC) phenotype is predictable in SIVmac239-infected Indian rhesus macaques (RMs), with approximately 50% of Mamu-B*08+ RMs and 20% of Mamu-B*17+ RMs becoming ECs. Despite extensive characterization of EC-associated CTLs in HIV/SIV-infected individuals, the precise mechanistic basis of elite control remains unknown. Because EC and non-EC viral load trajectories begin diverging by day 14 post-infection, we hypothesized that hyperacute innate immune responses may contribute to viremic control.MethodsTo gain insight into the immunological factors involved in the determination of EC status, we vaccinated 16 Mamu-B*08+ RMs with Vif and Nef to elicit EC-associated CTLs, then subjected these 16 vaccinees and an additional 16 unvaccinated Mamu-B*08+ controls to repeated intrarectal SIVmac239 challenges. We then performed whole-blood transcriptomic analysis of all 32 SIVmac239-infected Mamu-B*08+ RMs and eight SIVmac239-infected Mamu-B*08– RMs during the first 14 days of infection.ResultsVaccination did not provide protection against acquisition, but peak and setpoint viremia were significantly lower in vaccinees relative to controls. We did not identify any meaningful correlations between vaccine-induced CTL parameters and SIVmac239 acquisition rate or chronic-phase viral loads. Ultimately, 13 of 16 vaccinees (81%) and 7 of 16 controls (44%) became ECs (viremia ≤ 10,000 vRNA copies/mL plasma for ≥ 4 weeks). We identified subsets of immunomodulatory genes differentially expressed (DE) between RM groupings based on vaccination status, EC status, and MHC class I genotype. These DE genes function in multiple innate immune processes, including the complement system, cytokine/chemokine signaling, pattern recognition receptors, and interferon-mediated responses.DiscussionA striking difference in the kinetics of differential gene expression among our RM groups suggests that Mamu-B*08-associated elite control is characterized by a robust, rapid innate immune response that quickly resolves. These findings indicate that, despite the association between MHC class I genotype and elite control, innate immune factors in hyperacute SIV infection preceding CTL response development may facilitate the establishment of the EC phenotype.

Published
2024
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7. No evidence for ongoing replication on ART in SIV-infected macaques

Author

Taina T. Immonen, Christine M. Fennessey, Leslie Lipkey, Laura Newman, Agatha Macairan, Marjorie Bosche, Nora Waltz, Gregory Q. Del Prete, Jeffrey D. Lifson, and Brandon F. Keele

Subjects
Science
Abstract

Abstract The capacity of HIV-1 to replicate during optimal antiretroviral therapy (ART) is challenging to assess directly. To gain greater sensitivity to detect evolution on ART, we used a nonhuman primate (NHP) model providing precise control over the level of pre-ART evolution and more comprehensive analyses than are possible with clinical samples. We infected 21 rhesus macaques (RMs) with the barcoded virus SIVmac239M and initiated ART early to minimize baseline genetic diversity. RMs were treated for 285–1200 days. We used several tests of molecular evolution to compare 1352 near-full-length (nFL) SIV DNA single genome sequences from PBMCs, lymph nodes, and spleen obtained near the time of ART initiation and those present after long-term ART, none of which showed significant changes to the SIV DNA population during ART in any animal. To investigate the possibility of ongoing replication in unsampled putative tissue sanctuaries during ART, we discontinued treatment in four animals and confirmed that none of the 336 nFL SIV RNA sequences obtained from rebound plasma viremia showed evidence of evolution. The rigorous nature of our analyses reinforced the emerging consensus of a lack of appreciable ongoing replication on effective ART and validates the relevance of this NHP model for cure studies.

Published
2024
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8. AImedReport: A Prototype Tool to Facilitate Research Reporting and Translation of Artificial Intelligence Technologies in Health Care

Author

Tracey A. Brereton, MS, Momin M. Malik, PhD, MS, MSc, Lauren M. Rost, PhD, MS, Joshua W. Ohde, PhD, Lu Zheng, PhD, MS, Kristelle A. Jose, MS, Kevin J. Peterson, PhD, MS, David Vidal, JD, Mark A. Lifson, PhD, Joe Melnick, BS, Bryce Flor, BS, Jason D. Greenwood, MD, MS, Kyle Fisher, MPA, and Shauna M. Overgaard, PhD

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Published
2024
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9. Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence.

Author

Benjamin Varco-Merth, Morgan Chaunzwa, Derick M Duell, Alejandra Marenco, William Goodwin, Rachel Dannay, Michael Nekorchuk, Danica Shao, Kathleen Busman-Sahay, Christine M Fennessey, Lorna Silipino, Michael Hull, William J Bosche, Randy Fast, Kelli Oswald, Rebecca Shoemaker, Rachele Bochart, Rhonda MacAllister, Caralyn S Labriola, Jeremy V Smedley, Michael K Axthelm, Miles P Davenport, Paul T Edlefsen, Jacob D Estes, Brandon F Keele, Jeffrey D Lifson, Sharon R Lewin, Louis J Picker, and Afam A Okoye

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

Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes. However, treatment was followed by proliferation and reconstitution of CD4+ T cells in blood, and despite ongoing ART, levels of cell-associated SIV DNA in blood and lymphoid tissues were not substantially different between alemtuzumab-treated and control RM after immune cell reconstitution, irrespective of the time of alemtuzumab treatment. Upon ART cessation, 19 of 22 alemtuzumab-treated RM and 13 of 13 controls rebounded with no difference in the time to rebound between treatment groups. Time to rebound and reactivation rate was associated with plasma viral loads (pVLs) at time of ART initiation, suggesting lymphocyte depletion had no durable impact on the RCVR. However, 3 alemtuzumab-treated RM that had lowest levels of pre-ART viremia, failed to rebound after ART withdrawal, in contrast to controls with similar levels of SIV replication. These observations suggest that alemtuzumab therapy has little to no ability to reduce well-established RCVRs but may facilitate RCVR destabilization when pre-ART virus levels are particularly low.

Published
2024
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10. Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques

Author

Benjamin N. Bimber, Justine Sunshine, G. W. McElfresh, Jason S. Reed, Reese Pathak, Katherine B. Bateman, Colette M. Hughes, Roxanne M. Gilbride, Julia C. Ford, David Morrow, Jeffrey D. Lifson, Jonah B. Sacha, Scott G. Hansen, and Louis J. Picker

Subjects
SIV, viral escape, CMV vaccine vector, viral sequence analysis, HIV/SIV, Immunologic diseases. Allergy, RC581-607
Abstract

Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations. While low level viral mutations accumulated in all animals by 28 days-post-challenge, which is after the establishment of viral control in protected animals, the dominant circulating virus in virtually all unprotected RMs was nearly identical to the challenge stock, and there was no difference in mutation patterns between this cohort and unvaccinated controls. These data definitively demonstrate that viral mutation does not explain lack of viral control in RMs not protected by RhCMV/SIV vaccination. We further demonstrate that during chronic infection RhCMV/SIV vaccinated RMs do not acquire escape mutation in epitopes targeted by RhCMV/SIV, but instead display mutation in canonical MHC-Ia epitopes similar to unvaccinated RMs. This suggests that after the initial failure of viral control, unconventional T cell responses induced by 68-1 RhCMV/SIV vaccination do not exert strong selective pressure on systemically replicating SIV.

Published
2024
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12. Simplifying QCD event generation with chirality flow, reference vectors and spin directions

Author

Emil Boman, Andrew Lifson, Malin Sjodahl, Adam Warnerbring, and Zenny Wettersten

Subjects
Automation, Chiral Lagrangian, Specific QCD Phenomenology, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract The chirality-flow formalism, combined with good choices of gauge reference vectors, simplifies tree-level calculations to the extent that it is often possible to write down amplitudes corresponding to Feynman diagrams immediately. It has also proven to give a very sizable speedup in a proof of concept implementation of massless tree-level QED in MadGraph5_aMC@NLO. In the present paper we extend this analysis to QCD, including massive quarks. We define helicity-dependent versions of the gluon vertices, derive constraints on the spinor structure of propagating gluons, and explore the Schouten identity to simplify the four-gluon vertex further. For massive quarks, the chirality-flow formalism sheds light on how to exploit the freedom to measure spin along any direction to shorten the calculations. Overall, this results in a clear speedup for treating the Lorentz structure at high multiplicities.

Published
2024
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14. AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques

Author

Dashti, Amir, Sukkestad, Sophia, Horner, Anna M., Neja, Margaret, Siddiqi, Zain, Waller, Chevaughn, Goldy, Jordan, Monroe, Dominique, Lin, Alice, Schoof, Nils, Singh, Vidisha, Mavigner, Maud, Lifson, Jeffrey D., Deleage, Claire, Tuyishime, Marina, Falcinelli, Shane D., King, Hannah A. D., Ke, Ruian, Mason, Rosemarie D., Archin, Nancie M., Dunham, Richard M., Safrit, Jeffrey T., Jean, Sherrie, Perelson, Alan S., Margolis, David M., Ferrari, Guido, Roederer, Mario, Silvestri, Guido, and Chahroudi, Ann

Published
2023
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16. Development and preliminary testing of Health Equity Across the AI Lifecycle (HEAAL): A framework for healthcare delivery organizations to mitigate the risk of AI solutions worsening health inequities.

Author

Jee Young Kim, Alifia Hasan, Katherine C Kellogg, William Ratliff, Sara G Murray, Harini Suresh, Alexandra Valladares, Keo Shaw, Danny Tobey, David E Vidal, Mark A Lifson, Manesh Patel, Inioluwa Deborah Raji, Michael Gao, William Knechtle, Linda Tang, Suresh Balu, and Mark P Sendak

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

The use of data-driven technologies such as Artificial Intelligence (AI) and Machine Learning (ML) is growing in healthcare. However, the proliferation of healthcare AI tools has outpaced regulatory frameworks, accountability measures, and governance standards to ensure safe, effective, and equitable use. To address these gaps and tackle a common challenge faced by healthcare delivery organizations, a case-based workshop was organized, and a framework was developed to evaluate the potential impact of implementing an AI solution on health equity. The Health Equity Across the AI Lifecycle (HEAAL) is co-designed with extensive engagement of clinical, operational, technical, and regulatory leaders across healthcare delivery organizations and ecosystem partners in the US. It assesses 5 equity assessment domains-accountability, fairness, fitness for purpose, reliability and validity, and transparency-across the span of eight key decision points in the AI adoption lifecycle. It is a process-oriented framework containing 37 step-by-step procedures for evaluating an existing AI solution and 34 procedures for evaluating a new AI solution in total. Within each procedure, it identifies relevant key stakeholders and data sources used to conduct the procedure. HEAAL guides how healthcare delivery organizations may mitigate the potential risk of AI solutions worsening health inequities. It also informs how much resources and support are required to assess the potential impact of AI solutions on health inequities.

Published
2024
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17. Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir

Author

Brandon F. Keele, Afam A. Okoye, Christine M. Fennessey, Benjamin Varco-Merth, Taina T. Immonen, Emek Kose, Andrew Conchas, Mykola Pinkevych, Leslie Lipkey, Laura Newman, Agatha Macairan, Marjorie Bosche, William J. Bosche, Brian Berkemeier, Randy Fast, Mike Hull, Kelli Oswald, Rebecca Shoemaker, Lorna Silipino, Robert J. Gorelick, Derick Duell, Alejandra Marenco, William Brantley, Jeremy Smedley, Michael Axthelm, Miles P. Davenport, Jeffrey D. Lifson, and Louis J. Picker

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Published
2024

18. Chronic SIV-Induced neuroinflammation disrupts [CCR7.sup.+] [CD4.sup.+] T cell immunosurveillance in the rhesus macaque brain

Author

Elizaldi, Sonny R., Hawes, Chase E., Verma, Anil, Lakshmanappa, Yashavanth Shaan, Dinasarapu, Ashok R., Schlegel, Brent T., Rajasundaram, Dhivyaa, Li, Jie, Durbin-Johnson, Blythe P., Ma, Zhong-Min, Pal, Pabitra B., Beckman, Danielle, Ott, Sean, Raeman, Reben, Lifson, Jeffrey, Morrison, John H., and Iyer, Smita S.

Subjects
Chemokine receptors -- Physiological aspects -- Health aspects, CD4 lymphocytes -- Physiological aspects -- Health aspects, Central nervous system diseases -- Development and progression -- Causes of -- Models, Simian immunodeficiency virus -- Physiological aspects -- Health aspects, Health care industry
Abstract

[CD4.sup.+] T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-Seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of [CCR7.sup.+] [CD4.sup.+] T cells resembling lymph node central memory ([T.sub.CM]) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of [T.sub.CM]. Brain [CCR7.sup.+] [CD4.sup.+] T cells exhibited recall proliferation and interleukin- 2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering [T.sub.CM] cells in lymph nodes using FTY720 led to reduced [CCR7.sup.+] [CD4.sup.+] T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain [CCR7.sup.+] [CD4.sup.+] T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for [CCR7.sup.+] [CD4.sup.+] T cells in CNS immune surveillance, and their decline during chronic SIV highlights their responsiveness to neuroinflammation., Introduction Antigen-experienced T lymphocyte subsets, encompassing central ([T.sub.CM]), effector ([T.sub.EM]), and tissue resident memory T cells ([T.sub.RM]), actively survey and inhabit major organ systems, contributing to immune defense and tissue [...]

Published
2024
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21. The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection

Author

Alexandra Melton, Lori A. Rowe, Toni Penney, Clara Krzykwa, Kelly Goff, Sarah E. Scheuermann, Hunter J. Melton, Kelsey Williams, Nadia Golden, Kristyn Moore Green, Brandon Smith, Kasi Russell-Lodrigue, Jason P. Dufour, Lara A. Doyle-Meyers, Faith Schiro, Pyone P. Aye, Jeffery D. Lifson, Brandon J. Beddingfield, Robert V. Blair, Rudolf P. Bohm, Jay K. Kolls, Jay Rappaport, James A. Hoxie, and Nicholas J. Maness

Subjects
SARS-CoV-2, HIV/SIV, coinfection, Microbiology, QR1-502
Abstract

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Published
2024
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22. Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge.

Author

Michael W Grunst, Hwi Min Gil, Andres G Grandea, Brian J Snow, Raiees Andrabi, Rebecca Nedellec, Iszac Burton, Natasha M Clark, Sanath Kumar Janaka, Nida K Keles, Ryan V Moriarty, Andrea M Weiler, Saverio Capuano, Christine M Fennessey, Thomas C Friedrich, Shelby L O'Connor, David H O'Connor, Aimee T Broman, Brandon F Keele, Jeffrey D Lifson, Lars Hangartner, Dennis R Burton, and David T Evans

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

Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously identified an antibody to the variable 2 (V2) apex of the HIV-1 Env trimer (PGT145) that potently directs the lysis of SIV-infected cells by NK cells but poorly neutralizes SIV infectivity. To determine if ADCC is sufficient for protection, separate groups of six rhesus macaques were treated with PGT145 or a control antibody (DEN3) by intravenous infusion followed five days later by intrarectal challenge with SIVmac239. Despite high concentrations of PGT145 and potent ADCC activity in plasma on the day of challenge, all animals became infected and viral loads did not differ between the PGT145- and DEN3-treated animals. To determine if PGT145 can protect against a neutralization-sensitive virus, two additional groups of six macaques were treated with PGT145 and DEN3 and challenged with an SIVmac239 variant with a single amino acid change in Env (K180S) that increases PGT145 binding and renders the virus susceptible to neutralization by this antibody. Although there was no difference in virus acquisition, peak and chronic phase viral loads were significantly lower and time to peak viremia was significantly delayed in the PGT145-treated animals compared to the DEN3-treated control animals. Env changes were also selected in the PGT145-treated animals that confer resistance to both neutralization and ADCC. These results show that ADCC is not sufficient for protection by this V2-specific antibody. However, protection may be achieved by increasing the affinity of antibody binding to Env above the threshold required for neutralization.

Published
2024
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23. Deep analysis of CD4 T cells in the rhesus CNS during SIV infection.

Author

Sonny R Elizaldi, Anil Verma, Zhong-Min Ma, Sean Ott, Dhivyaa Rajasundaram, Chase E Hawes, Yashavanth Shaan Lakshmanappa, Mackenzie L Cottrell, Angela D M Kashuba, Zandrea Ambrose, Jeffrey D Lifson, John H Morrison, and Smita S Iyer

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

Virologic suppression with antiretroviral therapy (ART) has significantly improved health outcomes for people living with HIV, yet challenges related to chronic inflammation in the central nervous system (CNS)-known as Neuro-HIV- persist. As primary targets for HIV-1 with the ability to survey and populate the CNS and interact with myeloid cells to co-ordinate neuroinflammation, CD4 T cells are pivotal in Neuro-HIV. Despite their importance, our understanding of CD4 T cell distribution in virus-targeted CNS tissues, their response to infection, and potential recovery following initiation of ART remain limited. To address these gaps, we studied ten SIVmac251-infected rhesus macaques using an ART regimen simulating suboptimal adherence. We evaluated four macaques during the acute phase pre-ART and six during the chronic phase. Our data revealed that HIV target CCR5+ CD4 T cells inhabit both the brain parenchyma and adjacent CNS tissues, encompassing choroid plexus stroma, dura mater, and the skull bone marrow. Aligning with the known susceptibility of CCR5+ CD4 T cells to viral infection and their presence within the CNS, high levels of viral RNA were detected in the brain parenchyma and its border tissues during acute SIV infection. Single-cell RNA sequencing of CD45+ cells from the brain revealed colocalization of viral transcripts within CD4 clusters and significant activation of antiviral molecules and specific effector programs within T cells, indicating CNS CD4 T cell engagement during infection. Acute infection led to marked imbalance in the CNS CD4/CD8 ratio which persisted into the chronic phase. These observations underscore the functional involvement of CD4 T cells within the CNS during SIV infection, enhancing our understanding of their role in establishing CNS viral presence. Our findings offer insights for potential T cell-focused interventions while underscoring the challenges in eradicating HIV from the CNS, particularly in the context of sub-optimal ART.

Published
2023
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24. Changing character and waning impact of COVID-19 at a tertiary centre in Cape Town, South Africa

Author

Lucas E. Hermans, Petro Booysen, Linda Boloko, Marguerite Adriaanse, Timothy J. de Wet, Aimee R. Lifson, Naweed Wadee, Nectarios Papavarnavas, Gert Marais, Nei-yuan Hsiao, Michael-Jon Rosslee, Gregory Symons, Gregory L. Calligaro, Arash Iranzadeh, Robert J. Wilkinson, Ntobeko A.B. Ntusi, Carolyn Williamson, Mary-Ann Davies, Graeme Meintjes, and Sean Wasserman

Subjects
sars-cov-2, covid-19, omicron, delta, clinical characteristics, observational study, Infectious and parasitic diseases, RC109-216
Abstract

Background: The emergence of genetic variants of SARS-CoV-2 was associated with changing epidemiological characteristics throughout coronavirus disease 2019 (COVID-19) pandemic in population-based studies. Individual-level data on the clinical characteristics of infection with different SARS-CoV-2 variants in African countries is less well documented. Objectives: To describe the evolving clinical differences observed with the various SARS-CoV-2 variants of concern and compare the Omicron-driven wave in infections to the previous Delta-driven wave. Method: We performed a retrospective observational cohort study among patients admitted to a South African referral hospital with COVID-19 pneumonia. Patients were stratified by epidemiological wave period, and in a subset, the variants associated with each wave were confirmed by genomic sequencing. Outcomes were analysed by Cox proportional hazard models. Results: We included 1689 patients were included, representing infection waves driven predominantly by ancestral, Beta, Delta and Omicron BA1/BA2 BA4/BA5 variants. Crude 28-day mortality was 25.8% (34/133) in the Omicron wave period versus 37.1% (138/374) in the Delta wave period (hazard ratio [HR] 0.68 [95% CI 0.47–1.00] p = 0.049); this effect persisted after adjustment for age, gender, HIV status and presence of cardiovascular disease (adjusted HR [aHR] 0.43 [95% CI 0.28–0.67] p 0.001). Hospital-wide SARS-CoV-2 admissions and deaths were highest during the Delta wave period, with a decoupling of SARS-CoV-2 deaths and overall deaths thereafter. Conclusion: There was lower in-hospital mortality during Omicron-driven waves compared with the prior Delta wave, despite patients admitted during the Omicron wave being at higher risk. Contribution: This study summarises clinical characteristics associated with SARS-CoV-2 variants during the COVID-19 pandemic at a South African tertiary hospital, demonstrating a waning impact of COVID-19 on healthcare services over time despite epidemic waves driven by new variants. Findings suggest the absence of increasing virulence from later variants and protection from population and individual-level immunity.

Published
2023
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25. Long-acting lenacapavir protects macaques against intravenous challenge with simian-tropic HIV

Author

Swanstrom, Adrienne E., Gorelick, Robert J., Welker, Jorden L., Schmidt, Fabian, Lu, Bing, Wang, Kelly, Rowe, William, Breed, Matthew W., Killoran, Kristin E., Kramer, Joshua A., Donohue, Duncan, Roser, James D., Bieniasz, Paul D., Hatziioannou, Theodora, Pyle, Cathi, Thomas, James A., Trubey, Charles M., Zheng, Jim, Blair, Wade, Yant, Stephen R., Lifson, Jeffrey D., and Del Prete, Gregory Q.

Published
2023
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27. Cryo-EM structures of prefusion SIV envelope trimer

Author

Gorman, Jason, Wang, Chunyan, Mason, Rosemarie D., Nazzari, Alexandra F., Welles, Hugh C., Zhou, Tongqing, Bess, Jr, Julian W., Bylund, Tatsiana, Lee, Myungjin, Tsybovsky, Yaroslav, Verardi, Raffaello, Wang, Shuishu, Yang, Yongping, Zhang, Baoshan, Rawi, Reda, Keele, Brandon F., Lifson, Jeffrey D., Liu, Jun, Roederer, Mario, and Kwong, Peter D.

Published
2022
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28. Improving colour computations in MadGraph5_aMC@NLO and exploring a $$1/N_c$$ 1 / N c expansion

Author

Andrew Lifson and Olivier Mattelaer

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract In this paper, we present an extension of MadGraph5_aMC@NLO which is able to evaluate tree-level QCD matrix-elements up to $$2\rightarrow 6$$ 2 → 6 (one more particle than before). To achieve this, we implemented Berends–Giele-like recursion, and re-implemented the way colour is computed such that we can now expand the colour matrix in powers of $$1/N_c$$ 1 / N c and truncate this expansion to a chosen order. For high multiplicity samples, even without truncating the colour matrix, the new implementation offers a speed gain compared to the previous MadGraph5_aMC@NLO code.

Published
2022
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29. Long-acting lenacapavir protects macaques against intravenous challenge with simian-tropic HIVResearch in context

Author

Adrienne E. Swanstrom, Robert J. Gorelick, Jorden L. Welker, Fabian Schmidt, Bing Lu, Kelly Wang, William Rowe, Matthew W. Breed, Kristin E. Killoran, Joshua A. Kramer, Duncan Donohue, James D. Roser, Paul D. Bieniasz, Theodora Hatziioannou, Cathi Pyle, James A. Thomas, Charles M. Trubey, Jim Zheng, Wade Blair, Stephen R. Yant, Jeffrey D. Lifson, and Gregory Q. Del Prete

Subjects
HIV, Pre-exposure prophylaxis, PrEP, Nonhuman primate, Macaque, Capsid, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Long-acting subcutaneous lenacapavir (LEN), a first-in-class HIV capsid inhibitor approved by the US FDA for the treatment of multidrug-resistant HIV-1 with twice yearly dosing, is under investigation for HIV-1 pre-exposure prophylaxis (PrEP). We previously derived a simian-tropic HIV-1 clone (stHIV-A19) that encodes an HIV-1 capsid and replicates to high titres in pigtail macaques (PTM), resulting in a nonhuman primate model well-suited for evaluating LEN PrEP in vivo. Methods: Lenacapavir potency against stHIV-A19 in PTM peripheral blood mononuclear cells in vitro was determined and subcutaneous LEN pharmacokinetics were evaluated in naïve PTMs in vivo. To evaluate the protective efficacy of LEN PrEP, naïve PTMs received either a single subcutaneous injection of LEN (25 mg/kg, N = 3) or vehicle (N = 4) 30 days before a high-dose intravenous challenge with stHIV-A19, or 7 daily subcutaneous injections of a 3-drug control PrEP regimen starting 3 days before stHIV-A19 challenge (N = 3). Findings: In vitro, LEN showed potent antiviral activity against stHIV-A19, comparable to its potency against HIV-1. In vivo, subcutaneous LEN displayed sustained plasma drug exposures in PTMs. Following stHIV-A19 challenge, while all vehicle control animals became productively infected, all LEN and 3-drug control PrEP animals were protected from infection. Interpretation: These findings highlight the utility of the stHIV-A19/PTM model and support the clinical development of long-acting LEN for PrEP in humans. Funding: Gilead Sciences as part of a Cooperative Research and Development Agreement between Gilead Sciences and Frederick National Lab; federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024/HHSN261201500003I; NIH grant R01AI078788.

Published
2023
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30. The Role of Artificial Intelligence Model Documentation in Translational Science: Scoping Review

Author

Tracey A Brereton, Momin M Malik, Mark Lifson, Jason D Greenwood, Kevin J Peterson, and Shauna M Overgaard

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Medical technology, R855-855.5
Abstract

BackgroundDespite the touted potential of artificial intelligence (AI) and machine learning (ML) to revolutionize health care, clinical decision support tools, herein referred to as medical modeling software (MMS), have yet to realize the anticipated benefits. One proposed obstacle is the acknowledged gaps in AI translation. These gaps stem partly from the fragmentation of processes and resources to support MMS transparent documentation. Consequently, the absence of transparent reporting hinders the provision of evidence to support the implementation of MMS in clinical practice, thereby serving as a substantial barrier to the successful translation of software from research settings to clinical practice. ObjectiveThis study aimed to scope the current landscape of AI- and ML-based MMS documentation practices and elucidate the function of documentation in facilitating the translation of ethical and explainable MMS into clinical workflows. MethodsA scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. PubMed was searched using Medical Subject Headings key concepts of AI, ML, ethical considerations, and explainability to identify publications detailing AI- and ML-based MMS documentation, in addition to snowball sampling of selected reference lists. To include the possibility of implicit documentation practices not explicitly labeled as such, we did not use documentation as a key concept but as an inclusion criterion. A 2-stage screening process (title and abstract screening and full-text review) was conducted by 1 author. A data extraction template was used to record publication-related information; barriers to developing ethical and explainable MMS; available standards, regulations, frameworks, or governance strategies related to documentation; and recommendations for documentation for papers that met the inclusion criteria. ResultsOf the 115 papers retrieved, 21 (18.3%) papers met the requirements for inclusion. Ethics and explainability were investigated in the context of AI- and ML-based MMS documentation and translation. Data detailing the current state and challenges and recommendations for future studies were synthesized. Notable themes defining the current state and challenges that required thorough review included bias, accountability, governance, and explainability. Recommendations identified in the literature to address present barriers call for a proactive evaluation of MMS, multidisciplinary collaboration, adherence to investigation and validation protocols, transparency and traceability requirements, and guiding standards and frameworks that enhance documentation efforts and support the translation of AI- and ML-based MMS. ConclusionsResolving barriers to translation is critical for MMS to deliver on expectations, including those barriers identified in this scoping review related to bias, accountability, governance, and explainability. Our findings suggest that transparent strategic documentation, aligning translational science and regulatory science, will support the translation of MMS by coordinating communication and reporting and reducing translational barriers, thereby furthering the adoption of MMS.

Published
2023
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31. Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

Author

Fangzhu Zhao, Zachary T. Berndsen, Nuria Pedreño-Lopez, Alison Burns, Joel D. Allen, Shawn Barman, Wen-Hsin Lee, Srirupa Chakraborty, Sandrasegaram Gnanakaran, Leigh M. Sewall, Gabriel Ozorowski, Oliver Limbo, Ge Song, Peter Yong, Sean Callaghan, Jessica Coppola, Kim L. Weisgrau, Jeffrey D. Lifson, Rebecca Nedellec, Thomas B. Voigt, Fernanda Laurino, Johan Louw, Brandon C. Rosen, Michael Ricciardi, Max Crispin, Ronald C. Desrosiers, Eva G. Rakasz, David I. Watkins, Raiees Andrabi, Andrew B. Ward, Dennis R. Burton, and Devin Sok

Subjects
Science
Abstract

SIVmac239 infection of macaques is a favored model of human HIV infection, but antibody-mediated protection for SIVmac239 is insufficiently understood. Here, Zhao and Berndsen et al isolated nAbs and confirmed protection against SIVmac239 infection in passive transfer studies in macaques. The nAb was used to provide the first high-resolution structure of a rhesus SIV trimer by CryoEM. Analysis of the glycosylation pattern of this SIV trimer suggests a denser glycan shield on Env for rhesus SIV compared to chimpanzee SIV or HIV-1, which partially explains the poor nAb response of rhesus macaques to SIVmac239 infection.

Published
2022
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32. Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques

Author

Maria Pino, Amélie Pagliuzza, M. Betina Pampena, Claire Deleage, Elise G. Viox, Kevin Nguyen, Inbo Shim, Adam Zhang, Justin L. Harper, Sadia Samer, Colin T. King, Barbara Cervasi, Kiran P. Gill, Stephanie Ehnert, Sherrie M. Jean, Michael L. Freeman, Jeffrey D. Lifson, Deanna Kulpa, Michael R. Betts, Nicolas Chomont, Michael M. Lederman, and Mirko Paiardini

Subjects
Science
Abstract

Although antiretroviral therapy (ART) is able to successfully suppress plasma viremia in most people living with HIV, ART withdrawal typically results in viral replication and rebound. Authors investigate the effect, in terms of delay in viral replication, and immune cell dynamics in lymphoid tissue, of fingolimod (FTY720) administration at the time of ART initiation in SIV-infected rhesus macaques.

Published
2022
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33. The relationship between the epigenetic aging biomarker “grimage” and lung function in both the airway and blood of people living with HIV: An observational cohort study

Author

Baker, J.V., Duprez, D., Carr, A., Hoy, J., Dolan, M., Telenti, A., Grady, C., Matthews, G., Rockstroh, J., Belloso, W.H., Kagan, J.M., Wright, E., Brew, B., Price, R.W., Robertson, K., Cysique, L., Kunisaki, K.M., Connett, J.E., Niewoehner, D.E., Endpoint Review Committee, Lifson, A., Davey, R.T., Jr., Gatell, J.M., Pedersen, C., Prineas, R., Worley, J., Hernández Cordero, Ana I, Yang, Chen Xi, Yang, Julia, Li, Xuan, Horvath, Steve, Shaipanich, Tawimas, MacIsaac, Julia, Lin, David, McEwen, Lisa, Kobor, Michael S., Guillemi, Silvia, Harris, Marianne, Lam, Wan, Lam, Stephen, Obeidat, Ma'en, Novak, Richard M., Hudson, Fleur, Klinker, Hartwig, Dharan, Nila, Montaner, Julio, Man, S.F. Paul, Kunisaki, Ken, Sin, Don D., and Leung, Janice M.

Published
2022
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34. Automating scattering amplitudes with chirality flow

Author

Andrew Lifson, Malin Sjödahl, and Zenny Wettersten

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract Recently we introduced the chirality-flow formalism, a method which builds on the spinor-helicity formalism and is inspired by the color-flow idea in QCD. With this formalism, Feynman rules and diagrams are simplified to the extent that it is often possible to immediately, by hand, write down a helicity amplitude given a Feynman diagram. In this paper we show that the method can also speed up numerical evaluation of scattering amplitudes by considering $$e^+ e^-$$ e + e - going to n photons in a MadGraph-based tree-level implementation. We find that the computation time is reduced by roughly a factor ten for six photons, and that it scales better with the number of external particles than the default MadGraph5_aMC@NLO implementation. This performance gain is in part attributed to the more compact Lorentz structures involved, and in part due to a transparent choice of gauge reference vectors which reduces the number of Feynman diagrams considered.

Published
2022
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35. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses

Author

Pan, Hongchao, Peto, Richard, Henao Restrepo, Ana Maria, Preziosi, Marie-Pierre, Sathiyamoorthy, Vasee, Karim, Quarraisha Abdool, Alejandria, Marissa, Hernàndez García, César, Kieny, Marie-Paule, Malekzadeh, Reza, Murthy, Srinivas, Reddy, K. Srinath, Periago, Mirta Roses, Hanna, Pierre Abi, Abutidze, Akaki, Ader, Florence, Al-Bader, Abdullah, Alhasawi, Almonther, Allum, Emma, Al Mawali, Adhra, Alotaibi, Athari, Alvarez- Moreno, Carlos, Appadoo, Sheila, Arts, Derk, Asiri, Abdullah, Aukrust, Pål, Barratt-Due, Andreas, Genetu Bayih, Abebe, Beaumont, Helena, Bellani, Samir, Benassi, Virginia, Bhargava, Balram, Branca, Mattia, Cappel-Porter, Heike, Cerrato, Nery, Cheick Haidara, Fadima, Chow, Ting Soo, Como, Nadia, Eustace, Joe, Gabunia, Tamar, García, Patricia, Godbole, Sheela, Gotuzzo, Eduardo, Griskevicius, Laimonas, Hamra, Rasha, Hassan, Mariam, Hassany, Mohamed, Hutton, David, Irmansyah, Irmansyah, Jancoriene, Ligita, Khamis, Faryal, Kirwan, Jana, Kumar, Suresh, Lennon, Peter, Lopardo, Gustavo, Lydon, Patrick, Magrini, Nicola, Manevska, Suzana, Manuel, Oriol, McGinty, Sybil, Medina, Marco, Mesa Rubio, Maria Lucia, Miranda Montoya, Maria Consuelo, Nel, Jeremy, Nunes, Estevao, Perola, Markus, Portoles, Antonio, Rasmin, Menaldi, Raza, Aun, Rees, Helen, Reges, Paula, Rogers, Chris, Salami, Kolawole, Salvadori, Marina, Sauermann, Mamatha, Sinani, Narvina, Sow, Samba, Sterne, Jonathan AC, Stevanovikj, Milena, Tacconelli, Evelina, Tavares Maltez, Fernando Manuel, Teferi, Mekonnen, Tikkinen, Kari, Trelle, Sven, Tsertsvadze, Tengiz, Zaid, Hala, Røttingen, John-Arne, Swaminathan, Soumya, Ryan, Michael, Gjermeni, Nevila, Meta, Esmeralda, Aguila, Damian, Alonso, Ignacio, Altamirano, Marcos, Alvarez, María, Alzola, Rodrigo, Arce, Veronica, Arribillaga, Patricia, Avila, Rafael, Balbuena, Juan, Barcelona, Laura, Barletta, José, Benedetti, María, Berdiñas, Verónica, Burgui, Julieta, Caimi, Sabrina, Carrillo, Juan, Carrizo, Juan, Castelli, Juan, Cazaux, Alexis, Cervellino, Flavia, Chalco, Angelo, Chediack, Viviana, Cunto, Eleonora, D'Amico, Nicolàs, de Vedia, Lautaro, Delgado, Carolina, Di Pilla, Debora, Díaz, Miguel, Díaz Aguiar, Pablo, Domínguez, Cecilia, Ellero, Leonor, Farina, Javier, Fernàndez, José, Ferreyra, Roxana, Filippi, María, Fogar, Carolina, Frare, Pablo, Giudiche, Celeste, Golikow, Mariana, Gomez, Maria Georgina, Hermida, Laura, Hurtado, Mariano, Jacobo, Mariela, Jaume, Martin, Laplume, Diego, Lescano, María, Lista, Nicolàs, Loiacono, Flavia, López, Ana Belen, Losso, Marcelo, Luna, Cecilia, Lupo, Sergio, Marianelli, Leonardo, Martin, Anabella, Masciottra, Florencia, Mykietiuk, Analía, Orellano, Lorena, Pachioli, Valeria, Padilla, María José, Pallavicini, Cecilia, Patroso, Jazmin, Perez Blanco, Luz, Presas, Jose Louis, Provenzano, Matias, Lavera, Lorena, Reichert, Viviana, Riveros, Florencia, Rodríguez, Alejandra, Rolon, María José, Salvay, Carolina, Simonetta, María, Sisto, Alicia, Themines, Sandra, Tito, Fernando, Toibaro, Javier, Torales, Graciela, Verón, Luciano, Vizzotti, Carla, Egle, Alexander, Greil, Richard, Joannidis, Michael, Altdorfer, Antoine, Belkhir, Leila, Fraipont, Vincent, Hites, Maya, Arruda, Erico, Breda, Giovanni, Colussi, Arthur, Corradi, Miran, Croda, Julio, Duani, Helena, João, Esaú, Machado, Elizabeth, Mello, Fernanda, Miranda Filho, Demócrito, Monteiro, Poliana, Nunes, Ceuci, Pereira Junior, Luiz Carlos, Pinto, Gustavo, Raboni, Sonia, Ramos, Marcelo, Ruffing, Leonardo, Santos, Valdilea, Souza, Tamara, Medeiros, Melissa, Schwarzbold, Alexandre, Ali, Karim, Azher, Tanweer, Bellemare, David, Binnie, Alexandra, Borgia, Sergio, Cavayas, Yiorgos Alexandros, Chagnon, Nicholas, Cheng, Matthew, Cloutier, Eve, Conly, John, Costiniuk, Cecilia, Daneman, Nick, Douglas, James, Downey, Catarina, Duan, Erick, Durand, Medeline, English, Shane, Farjou, George, Fera, Evadiki, Fontela, Patricia, Fowler, Rob, Fralick, Mike, Gamble, David Gregory, Geagea, Anna, Grant, Jennifer, Harrison, Luke, Havey, Thomas, Hoang, Holly, Kelly, Lauren, Keynan, Yoav, Khwaja, Kosar, Klein, Marina, Kolan, Christophe, Kronfli, Nadine, Lamontagne, Francois, Lee, Nelson, Lee, Todd, Lim, Rachel, Lostun, Alexandra, MacIntyre, Erika, Malhamé, Isabelle, Martin-Carrier, Francois, McGuinty, Marlee, Munan, Matthew, O'Neil, Conar, Ovakim, Daniel, Papenburg, Jesse, Parhar, Ken, Parvathy, SeemaNair, Perez-Patrigeon, Santiago, Rishu, Asgar, Rushton, Moira, Scherr, Kim, Schwartz, Kevin, Semret, Makeda, Silverman, Micahel, Singh, Ameeta, Sligl, Wendy, Smith, Stephanie, Somayaji, Ranjani, Tan, Darrell, Tran, Tuong-Vi, Tremblay, Alain, Tsang, Jennifer, Turgeon, Alexis, Vakil, Erik, Weatherald, Jason, Yansouni, Cedric, Zarychanski, Ryan, Aristizabal, Claudia, Bravo, Juan, Caicedo, Monica, Chacón, Julio, Garzón, Diego, Guevara, Fredy, Lozano-Gonzàlez, Silvia, Macareno, Hugo, Montañez-Ayala, Anita, Oñate, Jose, Rojas-Gambasica, Jose, Rosso, Fernando, Saavedra, Carlos, Valderrama, Sandra, Vàquiro-Herrera, Eliana, Varón-Vega, Fabio, Zuluaga, Ivan, Abdel Baki, Amin, Abdelbary, Akram, Abdel-Razek, Wael, Amin, Wagdi, Asem, Noha, Elassal, Gehan, Elshesheny, Marwa, Fathy, Mohamed, Fathy, Naglaa, Fayed, Notaila, Hammam, Ahmed, Hassany, Sahar, Ibrahim, Hamdy, Kamal, Ehab, Masoud, Hossam, Mohamed, Maryam, Mohamed Gouda, Abdullah, Moustafa, Ehab, Okasha, Shaimaa, Rafik, Ahmed, Said, Ahmed, Sedky, Asmaa, Solyman Kabil, Mohamed, Tarek, Sara, Tharwat, Ahmed, Zaky, Samy, Abegaz, Emawayish Tesema, Bekele, Zelalem Mekonnen, Asfaw, Filmona Mekuria, Tegegne, Netsanet Aragaw, Teklemariam, Miheret Fikre, Nigusse, Frehiwot Tamiru, Achalu, Daniel Legesse, Weldegergs, Shewit Tesfagabr, Huluka, Dawit Kebede, Tereda, Addisu Birhanu, Ala-Kokko, Tero, Delany, Jutta, Ekroos, Heikki, Hankkio, Riina, Haukipää, Mia, Hetemäki, Iivo, Holma, Pia, Holmberg, Ville, Horstia, Saana, Jalkanen, Ville, Jämsänen, Toni, Järventie, Juuso, Järvinen, Petrus, Kalliala, Ilkka, Kauma, Heikki, Kilpeläinen, Tuomas, Kreivi, Hanna-Riikka, Kuitunen, Ilari, Lamminmäki, Satu, Mäkinen, Laura, Mäntylä, Jarkko, Mattila, Tiina, Myllärniemi, Marjukka, Niskanen, Joni, Nykänen, Taina, Nyqvist, Miro, Paajanen, Juuso, Partanen, Terhi, Patovirta, Riitta-Liisa, Paukkeri, Erja-Leena, Puusti, Emmi, Renner, Andreas, Reponen, Emma, Risku, Sari, Rosberg, Tuomas, Rutanen, Jarno, Säilä, Petrus, Salonen, Päivi, Sinisalo, Marjatta, Sivenius, Katariina, Tuominen, Susanna, Aboab, Jerone, Alfaiate, Toni, Andrejak, Claire, Andreu, Pascal, Belhadi, Drifa, Benezit, Francois, Botelho-Nevers, Elisabeth, Bouadma, Lila, Bougon, David, Bouiller, Kevin, Bounes, Fanny, Boyer, Alexandre, Bruel, Cédric, Buffet, Alexandre, Burdet, Charles, Cazanave, Charles, Chabertier, Cyrille, Clere-Jehl, Rapahel, Costagliola, Dominique, Courjon, Johan-Victor, Crockett, Flora, Danion, Francois, Dechanet, Aline, Dellamonica, Jean, Delmas, Christelle, Diallo, Alpha, Djossou, Felix, Dubost, Clement, Dupont, Axelle, Epaulard, Olivier, Faure, Emmmanuel, Faure, Karine, Fayol, Antoine, Figueiredo, Samy, Fougerou, Claire, Gaborit, Benjamin, Gaci, Rostane, Gagneux-Brunon, Amandine, Gallien, Sebastien, Garot, D, Goehringer, Francois, Gruson, Didier, Hinschberger, Olivier, Hulot, Jean-Sebastien, Jaureguiberry, Stephane, Jean-Michel, Vanessa, Kerneis, Solen, Kimmoun, Antoine, Klouche, Kada, Lachatre, Marie, Lacombe, Karine, Laine, Fabrice, Lanoix, Jean Philippe, Laribi, Samira, Launay, Odile, Laviolle, Bruno, Le Moing, Vincent, Le Pavec, Jerome, Lebeaux, David, Leroy, Sylvie, Lescure, Xavier, Livrozet, Marine, Makinson, Alain, Malvy, Denis, Marquette, Charles-Hugo, Martin-Blondel, Guillaume, Mayaux, Julien, Mekontso Dessap, Armand, Mentre, France, Mercier, Noemie, Meziani, Ferhat, Molina, Jean Michel, Mootien, Yoganaden, Mourvillier, Bruno, Navellou, Jean Christoph, Noret, M, Peiffer- Smadja, Nathan, Peytavin, Gilles, Pialoux, Gilles, Pilmis, Benoît, Piroth, Lionel, Poindron, Vincent, Poissy, Julien, Pourcher, Valerie, Quenot, Jean Pierre, Raffi, Francois, Reignier, Jean, Richard, Jean Christoph, Robert, Céline, Saillard, Juliette, Sayre, Naomi, Senneville, Eric, Stefan, Francois, Tellier, Marie Capucine, Terzi, Nicolas, Textoris, Julien, Thiery, Guillame, Timsit, Jean Francois, Tolsma, Violaine, Tubiana, Sarah, Wallet, Florent, Yazdanpanah, Yazdan, Zerbib, Yoann, Aguilar, Carlos, Erazo, Laura, Fiallos, Angel, Figueroa, Rosbinda, Flores, Juan Jose, Melendez, Lesddyy, Moncada, Wendy, Abraham, Ooriapadickal Cherian, Acharya, Chetankumar, Aedula, Vinaya Sekhar, Aggarwal, Richa, Agrawal, Nishant, Agrawal, Umang, Agrawal, Abhishekh, Ahmad, Mohammad, Atal, Shubham, Babu, Avinash, Baidya, Dalim Kumar, Balachandran, Amith, Bangar, Rakhee, Bhadade, Rakesh, Bhandari, Sudhir, Bhapal, Meghavi, Bhardwaj, Pankaj, Bhati, Gaurav, Bhatia, Pradeep, Bhatt, Krishnakant, Bingi, Thrilok Chander, Borse, Rohidas, Buch, Vyom, Chand, Dipti, Chandwani, Ashish, Charan, Jaykaran, Chaudhari, Mayur, Chaudhari, Kirti, Chaudhary, Vipul, Chauhan, Nishant, Chikara, Gaurav, Daswani, Bharti, de Souza, Rosemarie, Desai, Chetna, Divakar, Balusamy, Divhare, Sujeet, Dorairajan, Suresh Kumar, Dutt, Naveen, Ethirajan, Therani Rajan, Gamit, Amit, Gamit, Sweta, Garg, Mahendra, Goenka, Ajay, Goenka, Aniket, Guleria, Randeep, Gupta, Paras, Gupta, Nivedita, Gupta, Madhur, Harde, Minal, Ingle, Vaibhav, Iyer, Shivkumar, Jamalapuram, Vaishnavi, Jayanthi, Rangarajan, Joshi, Rajnish, Kadam, Abhijeet, Kalakuntla, Hemanth, Kalikar, Mrunalini, Kalme, Sayali, Kamble, Suchit, Kant, Ravi, Kantharia, Bansari, Kashikar, Arundhati, Kavishvar, Abhay, Kayina, Choro Athipro, Kerkar, Pranali, Khadanga, Sagar, Khandare, Sagar, Kokate, Pranjali, Komathi, Jayavelu, Krishnan, Vijay, Krishnan, Jayasree, Krishnan, Sumitra, Kulur Mukhyaprana, Sudha, Kumarasamy, N, Mahavar, Sunil, Maitra, Souvik, Majumdar, Falguni, Malhotra, Supriya, Mamulwar, Megha, Malini, Padma, Marwah, Vikas, Maurya, Akhilesh, Mehta, Kedar, Mesipogu, Rajarao, Misra, Shobha, Mitra, Sajal, Mittal, Ankit, Mohan, Bharathi, Momin, Mohmmedirfan, Nag, Vijaya, Nagarajan, Ramakrishnan, Nagmani, Kammili, Narlawar, Uday, Natarajan, Gopalakrishnan, Nischal, Neeraj, Ogale, Dhananjay, Palat, Paltial, Panda, Prasan, Panda, Samiran, Pandya, Amee, Parate, Rohit, Paritekar, Arunita, Patel, Parvati, Patel, Chetna, Patel, Sunaina, Patel, Vitan, Patel, Deep, Patel, Harshad, Patil, Girish, Peter, Deepu, Prasad, Durga, Purohit, Vimlesh, Rabindrarajan, Ebenezer, Ranganathan, Lakshmiarasimhan, Rao, Tushara, Rao, Chakradhara, Rathod, Chirag, Raval, Devang, Ray, Avik, Reddy, Kamini, Rege, Sujata, Revathi, Ayyasamy, Roy, Dhara, Saigal, Saurabh, Sane, Suvarna, Sangale, Shashi, Seetharaman, Krishnamoorthy, Selvamuthu, Poongulali, Seshaiah, Kurada Venkata, Shadrach, Benhur, Shah, Jignesh, Shah, Sonal, Sharma, Swati, Sharma, Raman, Sharma, Shrikant, Singh, Krishna, Singh, Anil, Singh, Arjeet, Singhai, Abhishek, Soneja, Manish, Soni, Kapil Dev, Subhan, Thasneem banu, Subramaniam, Sudharshini, Sudarsanam, Thambu David, Sudarsi, Ravindra Kumar, Suleman, Dawood, Suthar, Nilay, Talati, Shriraj, Tambe, Murlidhar, Tejomurtula, Tilak, Tirupakuzhi Vijayaraghavan, Bharatkumar, Trikha, Anjan, Trivedi, Aarti, Udwadia, Zarir, Upadhyay, Kamlesh, Vasava, Ashwin, Vasudevan, Damodaran, Velayudham, Rajendran, Venkatasubramanian, Ramasubramanian, Verma, Mamta, Waghmare, Rakesh, Waikar, Anushka, Wig, Naveet, Afrilia, Annisa Rizky, Amin, Muhammad, Arlinda, Dona, Avrina, Rossa, Bang, Lois, Djaharuddin, Irawaty, Djojo, Aryan, Driyah, Sri Laning, Erastuti, Mila, Fajarwati, Tetra, Harsini, Harsini, Hartantri, Yovita, Herman, Deddy, Isbaniah, Fathiyah, Karyana, Muhammad, Kusuma, Indra, Mahmudji, Harli Amir, Medison, Irvan, Nugroho, Agung, Nurhayati, Nurhayati, Opitasari, Cicih, Pitoyo, Ceva Wicaksono, Pradana, Antonius Arditya, Raharjo, Sofyan Budi, Rahmaini, Ade, Risniati, Yenni, Riyanto, Bambang Sigit, Sajinadiyasa, I Gede Ketut, Sari, Flora Eka, Sitompul, Pompini Agustina, Soedarsono, Soedarsono, Somia, I Ketut Agus, Sugiri, Yani Jane, Sugiyono, Retna Indah, Susanto, Nugroho Harry, Syarif, Armaji Kamaludi, Yulianto, Aris, Afsharian, Mandana, Akhavi Mirab, Atefehsadat, Amini, Fatemeh, Amini, Mahnaz, Ansarin, Khalil, Baba Mahmoodi, Farhang, Baghaei, Parvaneh, Barazandeh, Fateme, Bayani, Masomeh, Dastan, Farzaneh, Ebrahimpour, Soheil, Eghtesad, Sareh, Fallahi, Mohammad Javad, Fallahpoor Golmaee, Fatemeh, Foroghi Ghomi, Seyed Yaser, Ghadir, Mohammad Reza, Gheitani, Mina, Ghiasvand, Fereshteh, Hafizi Lotfabadi, Saied, Hakamifard, Atousa, Hashemi Madani, Shima Sadat, Hormati, Ahmad, Hosseini, Hamed, Janbakhsh, Alireza, Javanian, Mostafa, Joukar, Farahnaz, Kamali, Alireza, Karampour, Amin, Khajavirad, Nasim, Khodabakhshi, Behnaz, Khodadadi, Javad, Khodashahi, Rozita, Kiani Majd, Somaieh, Mahfoozi, Lida, Mahmoodiyeh, Behnam, Mansour-Ghanaei, Fariborz, Mansouri, Feizollah, Mesgarpour, Bita, Mesri, Mehdi, Mikaeili, Haleh, Miladi, Ronak, Moghadami, Mohsen, Mohamadi, Payam, Mohraz, Minoo, Mohseni Afshar, Zeinab, Moogahi, Sasan, Mousavi Anari, Seyed Alireza, Mozaffar, Seyyed Hassan, Mozdourian, Mahnaz, Najafipour, Reza, Najari, Hamidreza, Nazemiyeh, Masoud, Norouzi, Alireza, Pourkazemi, Aydin, Poustchi, Hossein, Saberhosseini, Seyedeh Naeimeh, Saberi, Marzieh, Saber-Moghaddam, Niloufar, Sadeghi, Anahita, Sadeghi Haddad Zavareh, Mahmoud, Sahraian, Mohammad Ali, Salahi, Mehrdad, Salehi, Mohammad Reza, Sarmadian, Hossein, Sayad, Babak, Shirani, Kiana, Shirvani, Maria, Shojaei, Daryanaz, Shokri, Mehran, Siami, Zeinab, Sima, Ali Reza, Soleimani, Alireza, Soltanmohammad, Saedeh, Tabarsi, Payam, Taghizadieh, Ali, Tavassoli, Samaneh, Varnasseri, Mehran, Vaziri, Siavash, Yadyad, Mohammad Jaafar, Yaghoubi, Shoeleh, Yazdanpanah, Yalda, Yousefi, Farid, Zamanian, Mohammad Hossein, Zand, Farid, Zare Hoseinzade, Elham, Bergin, Colm, Cotter, Aoife, de Barra, Eoghan, Jackson, Arthur, Laffey, John, McCarthy, Cormac, Muldoon, Eavan, Sadlier, Corinna, Maguire, Teresa, Angheben, Andrea, Bai, Francesca, Bandera, Alessandra, Barchiesi, Francesco, Bassetti, Matteo, Bisi, Luca, Bonfanti, Paolo, Calò, Federica, Campoli, Caterina, Canovari, Benedetta, Capetti, Amedeo, Castelli, Francesco, Cauda, Roberto, Cingolani, Antonella, Cocco, Nicolò, Coppola, Nicola, Corcione, Silvia, Cremonini, Eleonora, d'Arminio Monforte, Antonella, de Gaetano Donati, Katleen, De Nardo, Pasquale, De Rosa, Francesco Giuseppe, Degioanni, Maria, Della Siega, Paola, Di Bella, Stefano, Drera, Bruno, Focà, Emanuele, Fornabaio, Chiara, Galli, Massimo, Giacomazzi, Donatella, Gori, Andrea, Gustinetti, Giulia, Iannuzzi, Francesca, Kertusha, Blerta, Lamonica, Silvia, Lichtner, Miriam, Lupia, Tommaso, Luzzati, Roberto, Macera, Margherita, Menatti, Elisabetta, Merelli, Maria, Merlini, Esther, Monari, Caterina, Pan, Angelo, Pecori, Davide, Pezzani, Diletta, Riccardi, Niccolò, Rodari, Paola, Roldan, Eugenia, Rovere, Pierangelo, Rusconi, Stefano, Scabini, Silvia, Tascini, Carlo, Viale, Pierluigi, Vincenzi, Marcello, Zuccalà, Paola, Zucchi, Patrizia, Al-Roomi, Moudhi, Al-Sabah, Salman, Schrapp, Kelly, Hassoun, Mahmoud, Matar, Madonna, Dbouni, Oussaima, Yared, Nadine, Saliba, Michele, Farra, Anna, Riachi, Moussa, Zablockiene, Birute, Reuter, Jean, Staub, Therese, Ab Wahab, Suhaila, Chew, Chun Keat, Chua, Hock Hin, Goh, Pik Pin, Lee, Heng Gee, Leong, Chee Loon, Low, Lee Lee, Mak, Wen Yao, Mohamed Gani, Yasmin, Muhamad, Dzawani, Zaidan, Nor Zaila, Ducker, Camilla, Demiri, Ilir, Aballi, Saad, Berg, Åse, Blomberg, Bjørn, Dalgard, Olav, Dyrhol-Riise, Anne Ma, Eiken, Ragnhild, Ernst, Gernot, Hannula, Ranula, Haugli, Metter, Heggelund, Lars, Hoel, Hedda, Hoff, Dag Arne Lihaug, Holten, Aleksander Rygh, Johannessen, Asgeir, Kåsine, Trine, Kildal, Anders Benjamin, Kittang, Bård Reikvam, Nezvalova-Henriksen, Katerina, Olsen, Inge Christoffer, Olsen, Roy Bjørkolt, Skei, Nina Vibeche, Skudal, Hilde, Tholin, Birgitte, Thoresen, Lars, Trøseid, Marius, Tveita, Anders, Vinge, Leif, Ystrøm, Carl Magnus, Al Jahdhami, Issa, AlNaamani, Khalid, Al Balushi, Zakariya, Pandak, Nenad, Abbas, Salma, Akhtar, Nasim, Azam, Sumeyya, Begum, Dilshad, Hassan, Sadia, Herekar, Fivzia, Khan, Shahzaib, Khan, Ejaz Ahmed, Mahmood, Syed Faisal, Nasir, Nosheen, Rahim, Anum, Sarfaraz, Samreen, Shaikh, Qurat-ul-Ain, Sultan, Faisal, Walayat, Usman, Agurto-Lescano, Erika Cecilia, Alcantara-Díaz, Andrés Martín, Alva-Correa, Ana María, Alvarado-Moreno, José Gustavo, Ángeles-Padilla, Bethsabé, Arbañil-Huamàn, Hugo César, Ávila-Reyes, Pool Christopher, Azañero-Haro, Johan Alexander, Barreto-Rocchetti, Luis Guillermo, Benitez-Peche, Jorge Marko A., Bernal-Màlaga, Karla Hortencia, Cabrera-Portillo, Liliana Norma, Carazas-Chavarry, Reynaldo Javier, Càrcamo, Paloma Mariana, Casimiro-Porras, Indira Catalina, Castillo-Espinoza, Jhuliana, Chacaltana-Huarcaya, Jesús Norberto, Cornejo-Valdivia, Carla Raquel, Cruz-Chereque, Augusto, Del-Aguila-Torres, Keith Cayetano Marcelino, Díaz-Chipana, Erika, Flores-Valdez, Neil, Franco-Vàsquez, Rosanna Andrea, Gallegos-López, Roxana Consuelo, Gastiaburú-Rodriguez, Dauma Yesenia, Gianella-Malca, Gonzalo Ernesto, Gomero-Lopez, Andrés Alonso, Hercilla-Vàsquez, Luis Enrique, Hueda-Zavaleta, Miguel Ángel, Ibarcena-Llerena, Claudia Vanessa, Iberico-Barrera, Carlos Alberto, Inquilla-Castillo, Miguel Angel, Juàrez-Eyzaguirre, Jesus Alberto, Laca-Barrera, Manuel, León-Jiménez, Franco, Luna-Wilson, Carla Vanessa, Màlaga, German, Marin, Ricardo, Mejía-Cordero, Fernando, Mendoza-Laredo, Juan Arturo, Meregildo-Rodríguez, Edinson Dante, Miranda-Manrique, Gonzalo Francisco, Olivera-Chaupis, Marco, Ortega-Monasterios, Fatima Josefina, Otazú-Ybàñez, Jimmy Pedro, Paredes-Moreno, María Angélica, Peña-Mayorga, Claudia Ximena, Peña-Vàsquez, Olivia del Carmen, Peña-Villalobos, Alejandro, Ponce, Oscar J, Ponte-Fernandez, Katherin Estefania, Pro, Jose, Quispe-Nolazco, César Miguel, Ramos-Samanez, Manuel Efrain, Rojas-Murrugarra, Kory Mirtha, Samanez-Pérez, Jorge Mauro, Sànchez-Carrillo, Halbert Chrostian, Sànchez-Garavito, Epifanio, Sànchez-Sevillano, Ricardo Manuel, Sandoval-Manrique, Hernan, Santos-Revilla, Gabriela, Silva-Ramos, Julio Antonio, Solano-Ico, Manuel Alberto, Soto, Alonso, Sotomayor-Woolcott, Giannilu Michelle, Tapia-Orihuela, Ruben Kevin Arnold, Terrazas-Obregón, Carmen Sara, Terrones-Levano, Victor Francisco, Ticona-Huaroto, Cesar Eduardo, Torres-Ninapayta, Walter, Torres-Ruiz, Oscar Martin, Ugarte-Mercado, Dario, Vargas-Anahua, Orlando José, Vàsquez-Becerra, Ruben Dario, Vàsquez-Cerro, José Gabriel, Villegas-Chiroque, Miguel, Williams, Anna Larson, Yauri-Lazo, Randi Mauricio, Abad, Cybele Lara, Andales-Bacolcol, Silverose Ann, Arcegono, Marlon, Arches, Jamie, Astudillo, Mary Grace, Aventura, Emily, Awing, Arlyn, Bala, Mishelle Vonnabie, Bello, Jia An, Blanco, Peter, Benedicto, Jubert, Buno, Susana, Cabrera, Justine, Cajulao, Thea Pamela, Caoili, Janice, Casiple-Amsua, Lina, Catambing, Victor, Chin, Inofel, Chua, Ma. Bernadette, Chua, Mitzi Marie, Climacosa, Fresthel Monica, David-Wang, Aileen, De los Reyes, Virginia, Europa, Gilly May, Fernandez, Lenora, Francisco, Jorge, Garcia, Gerard, Garcia, Jemelyn, Gler, Maria Tarcela, Isidro, Marie Grace Dawn, Javier, Rozelle Jade, Kwek, Marion, Lansang, Mary Ann, Lee, Aileen, Li, Kingbherly, Llanes, Mark Ramon Victor, Llorin, Ryan, Macadato, Omar Khayyam, Malundo, Anna Flor, Mercado, Maria Elizabeth, Mujeres, Mercedes, Nepomuceno, Marisse, Ngo-Sanchez, Katha, Orden, Mary Claire, Pablo-Villamor, Maria Philina, Paez, Ruel Dionisio, Palmes, Patricio, Panaligan, Marion, Quinivista-Yoon, Jenny Mae, Ramos, Mary Shiela Ariola, Ramos -Penalosa, Christine, Reyes, Sheila Marie, Roa, Kathryn, Roman, Arthur Dessi, Rosario, Minette Claire, Roxas, Evalyn, Santos, Lourdes Ella Gonzales, Soldevilla, Helmar, Solante, Rontgene, Suaco, Jane, Tagarda, Daisy, Tang, Issa Rufina, Te, Bob, Teo, Dennis, Tibayan, Christopher John, Villalobos, Ralph Elvi, Ymbong, Duane Richard, Zabat, Gelza Mae, Batkova, Stepanka, Cardoso, Orlando, Garrote, Ana-Raquel, Lino, Sara, Manata, Maria-José, Pinheiro, Helder, Póvoas, Diana, Ramirez, Freddy, Seixas, Diana, Naji, Assem, Al Gethamy, M Al, AL-Mulaify, Mohammed Sami, Al Maghraby, Reem, Alrajhi, A, Al Sharidi, Aynaa, Alotaibi, Naif, AlShaharani, F, Barry, Mazin, Ghonem, Leen, Khalel, Anas, Kharaba, Ayman Mohammed, Alabdan, Lulwah, AlAbdullah, Mohammed Sharaf, Al Shabib, Abdullah, Bengu, Simangele, Bennet, Jacklyn, Dubula, Thozama, Howell, Pauline, Janse van Vuuren, Cloete, Kalla, Ismail, Lifson, Aimee, Maasdorp, Shaun, Magua, Nombulelo, Maluleke, Vongani, Mbhele, Nokuphiwa, Mdladla, Nathi, Mendelson, Mark, Menezes, Colin, Mwelase, Thando, Nchabeleng, Maphoshane, Palanee-Phillips, Thesla, Parker, Victoria, Rassool, Mohammed, Reeder, Paul, Sossen, Bianca, Steyn, Dewald, Tsitsi, Merika, van Blydenstein, Sarah Alex, Venter, Michelle, Van Vuuren, Janse, Venturas, Jacquie, Abad Pérez, Daniel, Abenza, Maria José, Alarcón-Payer, Carolina, Armero Garrigos, Eva, Arribas, Jose Ramon, Ascaso, Ana, Berenguer, Juan, Cabello-Clotet, Noemí, Chamorro Tojeiro, Sandra, Cuenca-Acevedo, Rafael, de la Calle, Fernando, Del Toro, Maria Dolores, Díaz Pollàn, Beatriz, Diez, Cristina, Esquillor-Rodrigo, María José, Estrada, Vicente, Fanciulli, Chiara, Fanjul, Francisco, Fernàndez de Orueta, Lucía, Ferre, Adrian, Ferreira Pasos, Eva Maria, Gainzarain-Arana, Juan-Carlos, Garcia, Felipe, García Deltoro, Miguel, Goikoetxea Agirre, Ane Josune, Gómez Barquero, Julia, Gomez-Huelgas, Ricardo, Gonzàlez Moraleja, Julio, Guijarro, Carlos, Gutierrez, Felix, Guzmàn, Jesús, Ibarguren, Maialen, Iribarren, Jose Antonio, Jerusalem, Koen, Juan Arribas, Arturo, Lalueza, A, Leone, Antonio, Lopez Azkarreta, Iñigo, Lozano-Martin, Daniel, Lucendo, Alfredo J, Luengo López, Mariella, Martín Oterino, JA, Masa, JF, Merino, Esperanza, Monge-Maillo, Begoña, Moran-Rodríguez, Miguel-Angel, Muñez Rubio, Elena, Muñoz Sanchez, Josefa, Nuñez Orantos, Maria Jose, Nuño, Enrique, Ortiz-De-Zarate-Ibarra, Zuriñe, Pagàn-Muñoz, Bàrbara, Paño-Pardo, José Ramón, Peñaranda, Maria, Pérez Chica, Gerardo, Pérez Fernàndez, AM, Pérez-López, Carmen, Polo San Ricardo, Victor, Portu-Zapirain, Joseba, Puchades, Francesco, Rivas Paterna, Ana Belen, Rodríguez Vidigal, Francisco F, Rodríguez-Baño, Jesus, Ruiz-Seco, Pilar, Ryan, Pablo, Saez-De-Adana, Ester, Salas, Rosario, Salavert Lletí, Miguel, Sandoval, Raquel, Toyas-Miazza, Carla, Valencia, Jorge, Vargas, Emilio, Velasco, Maria, Von Wichmann, Miguel Angel, Bosshard, Andreas, Calmy, Alexandra, Castro, Tiago, Cavassini, Matthias, Clerc, Olivier, Conen, Anna, Desbaillets, Nicolas, Desgranges, Florian, Duss, Francois, Emonet, Stephane, Erard, Veronique, Eyer, Myriam, Fayet-Mello, Aurélie, Flammer, Yvonne, Friedl, Andrée, Fulchini, Rosamaria, Furrer, Hansjakob, Garin, Nicolas, Gastberger, Salome, Greiner, Michael, Haefliger, David, Haubitz, Sebastian, Hoffmann, Matthias, Isenring, Egon, Jakopp, Barbara, Lampert, Markus, Marinosci, Annalisa, Martin, Yvonne, Petignat, Pierre-Auguste, Piso, Rein Jan, Prendki, Virginie, Rutishauser, Jonas, Schaefer, Elisabeth, Schmiedel, Yvonne, Schwery, Stefan, Stavropoulou, Elisavet, Stoeckle, Marcel, Suttels, Veronique, Thurnher, Maria Christine, van den Bogaart, Lorena, West, Emily, Wiegand, Jan, and Wiggli, Benedikt

Published
2022
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36. Acute-phase innate immune responses in SIVmac239-infected Mamu-B*08+ Indian rhesus macaques may contribute to the establishment of elite control.

Author

Rosen, Brandon C., Sawatzki, Kaitlin, Ricciardi, Michael J., Smith, Elise, Golez, Inah, Mauter, Jack T., Pedreño-López, Núria, Yrizarry-Medina, Aaron, Weisgrau, Kim L., Vosler, Logan J., Voigt, Thomas B., Louw, Johan J., Tisoncik-Go, Jennifer, Whitmore, Leanne S., Panayiotou, Christakis, Ghosh, Noor, Furlott, Jessica R., Parks, Christopher L., Desrosiers, Ronald C., and Lifson, Jeffrey D.

Subjects
AIDS, CYTOTOXIC T cells, SIMIAN immunodeficiency virus, HIV, PATTERN perception receptors
Abstract

Introduction: Spontaneous control of chronic-phase HIV/SIV viremia is often associated with the expression of specific MHC class I allotypes. HIV/SIV-specific CD8+ cytotoxic T lymphocytes (CTLs) restricted by these MHC class I allotypes appear to be critical for viremic control. Establishment of the elite controller (EC) phenotype is predictable in SIVmac239-infected Indian rhesus macaques (RMs), with approximately 50% of Mamu-B*08 + RMs and 20% of Mamu-B*17 + RMs becoming ECs. Despite extensive characterization of EC-associated CTLs in HIV/SIV-infected individuals, the precise mechanistic basis of elite control remains unknown. Because EC and non-EC viral load trajectories begin diverging by day 14 post-infection, we hypothesized that hyperacute innate immune responses may contribute to viremic control. Methods: To gain insight into the immunological factors involved in the determination of EC status, we vaccinated 16 Mamu-B*08 + RMs with Vif and Nef to elicit EC-associated CTLs, then subjected these 16 vaccinees and an additional 16 unvaccinated Mamu-B*08 + controls to repeated intrarectal SIVmac239 challenges. We then performed whole-blood transcriptomic analysis of all 32 SIVmac239-infected Mamu-B*08 + RMs and eight SIVmac239-infected Mamu-B*08 – RMs during the first 14 days of infection. Results: Vaccination did not provide protection against acquisition, but peak and setpoint viremia were significantly lower in vaccinees relative to controls. We did not identify any meaningful correlations between vaccine-induced CTL parameters and SIVmac239 acquisition rate or chronic-phase viral loads. Ultimately, 13 of 16 vaccinees (81%) and 7 of 16 controls (44%) became ECs (viremia ≤ 10,000 vRNA copies/mL plasma for ≥ 4 weeks). We identified subsets of immunomodulatory genes differentially expressed (DE) between RM groupings based on vaccination status, EC status, and MHC class I genotype. These DE genes function in multiple innate immune processes, including the complement system, cytokine/chemokine signaling, pattern recognition receptors, and interferon-mediated responses. Discussion: A striking difference in the kinetics of differential gene expression among our RM groups suggests that Mamu-B*08 -associated elite control is characterized by a robust, rapid innate immune response that quickly resolves. These findings indicate that, despite the association between MHC class I genotype and elite control, innate immune factors in hyperacute SIV infection preceding CTL response development may facilitate the establishment of the EC phenotype. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques

Author

Pino, Maria, Pagliuzza, Amélie, Pampena, M. Betina, Deleage, Claire, Viox, Elise G., Nguyen, Kevin, Shim, Inbo, Zhang, Adam, Harper, Justin L., Samer, Sadia, King, Colin T., Cervasi, Barbara, Gill, Kiran P., Ehnert, Stephanie, Jean, Sherrie M., Freeman, Michael L., Lifson, Jeffrey D., Kulpa, Deanna, Betts, Michael R., Chomont, Nicolas, Lederman, Michael M., and Paiardini, Mirko

Published
2022
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38. Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

Author

Zhao, Fangzhu, Berndsen, Zachary T., Pedreño-Lopez, Nuria, Burns, Alison, Allen, Joel D., Barman, Shawn, Lee, Wen-Hsin, Chakraborty, Srirupa, Gnanakaran, Sandrasegaram, Sewall, Leigh M., Ozorowski, Gabriel, Limbo, Oliver, Song, Ge, Yong, Peter, Callaghan, Sean, Coppola, Jessica, Weisgrau, Kim L., Lifson, Jeffrey D., Nedellec, Rebecca, Voigt, Thomas B., Laurino, Fernanda, Louw, Johan, Rosen, Brandon C., Ricciardi, Michael, Crispin, Max, Desrosiers, Ronald C., Rakasz, Eva G., Watkins, David I., Andrabi, Raiees, Ward, Andrew B., Burton, Dennis R., and Sok, Devin

Published
2022
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40. Serial Testing for SARS-CoV-2 and Virus Whole Genome Sequencing Inform Infection Risk at Two Skilled Nursing Facilities with COVID-19 Outbreaks — Minnesota, April–June 2020

Author

Minnesota Long-Term Care COVID-Response Group, Taylor, Joanne, Carter, Rosalind J., Lehnertz, Nicholas, Kazazian, Lilit, Sullivan, Maureen, Wang, Xiong, Garfin, Jacob, Diekman, Shane, Plumb, Matthew, Bennet, Mary Ellen, Hale, Tammy, Vallabhaneni, Snigdha, Namugenyi, Sarah, Carpenter, Deborah, Turner-Harper, Darlene, Booth, Marcus, Coursey, E. John, Martin, Karen, McMahon, Melissa, Beaudoin, Amanda, Lifson, Alan, Holzbauer, Stacy, Reddy, Sujan C., Jernigan, John A., and Lynfield, Ruth

Published
2020

41. Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody

Author

Asokan, Mangaiarkarasi, Dias, Joana, Liu, Cuiping, Maximova, Anna, Ernste, Keenan, Pegu, Amarendra, McKee, Krisha, Shi, Wei, Chen, Xuejun, Almasri, Cassandra, Promsote, Wanwisa, Ambrozak, David R., Gama, Lucio, Hu, Jianfei, Douek, Daniel C., Todd, John-Paul, Lifson, Jeffrey D., Fourati, Slim, Sekaly, Rafick P., Crowley, Andrew R., Ackerman, Margaret E., Ko, Sung Hee, Kilam, Divya, Boritz, Eli A., Liao, Laura E., Best, Katharine, Perelson, Alan S., Mascola, John R., and Koup, Richard A.

Published
2020

45. PP 8.1 – 00003 Optimization of the 5′ cap and untranslated regions enhances the immunogenicity of an mRNA-based therapeutic vaccine in SIV-infected rhesus macaques on ART

Author

W. Omange, B. Varco-Merth, A. Morenco, M.T. Chaunzwa, C. Nkoy, D. Duell, O. Fadeyi, M. Medina, S. Hoffmeister, W. Goodwin, R. Butler, Z. Etaki, H. Park, J. Smedley, M.K. Axhelm, S. Hansen, J. Lifson, J. Gergen, S. Rauch, B. Petsch, L.J. Picker, and A.A. Okoye

Subjects
Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Published
2022
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47. OP 2.4 – 00145 No Evidence of Ongoing Viral Replication in SIV-Infected Macaques on Combination Antiretroviral Therapy Initiated in the Chronic Phase of Infection Despite Elevated Residual Plasma Viral Loads

Author

G.Q. Del Prete, M. Nag, T. Immonen, C. Fennessey, W. Bosch, A. Conchas, A.E. Swanstrom, J. Lifson, B.F. Keele, A. Macairan, K. Oswald, R. Fast, R. Shoemaker, L. Silipino, M. Hull, D. Donohue, T. Malys, G. Muthua, M. Breed, and J. Kramer

Subjects
Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Published
2022
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49. PP 4.1 – 00013 Vaccine-mediated induction of elite control-associated CD8+ cytotoxic T lymphocytes in Mamu-B*08+ Indian rhesus macaques does not protect against intrarectal SIVmac239 acquisition

Author

B.C. Rosen, M.J. Ricciardi, Nuria Pedreño-Lopez, T.B. Voigt, F.D. Laurino, J.J. Louw, A. Yrizarry-Medina, C. Panayiotou, T. Newbolt, K.L. Weisgrau, J.D. Lifson, R.C. Desrosiers, E.G. Rakasz, and D.I. Watkins

Subjects
Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Published
2022
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