Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV.
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2025-10
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People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence for a Hybrid vs. Vaccine Group (baseline SARS-CoV-2-positive and one mRNA-1273 dose vs. negative and two doses). Using case-cohort sampling, antibody markers at enrolment (M0) and four weeks post-final vaccination (Peak) are assessed as immune correlates of COVID-19. For the Hybrid Group [n = 287 (195 PWH)], all M0 markers inversely correlate with COVID-19 through 230 days post-Peak, with 50% inhibitory dilution BA.4/5 neutralizing antibody titer (nAb-ID50 BA.4/5) the strongest and only independent correlate (HR per 10-fold increase=0.46, 95% CI 0.28, 0.75; P = 0.002). For the Vaccine Group [n = 115 (86 PWH)], Peak nAb-ID50 BA.4/5 correlates with reduced COVID-19 risk (1.9%, 1.1%, and 0.3% at titers 10, 100, and 1000 AU/ml) through 92, but not 165, days post-Peak. Using multivariable Cox analysis of binding and nAb, nAb titers predict COVID-19 in PWH. Two doses of a 100-µg Ancestral strain mRNA vaccine in baseline-SARS-CoV-2-negative individuals elicit sufficient cross-reacting Omicron antibodies to reduce COVID-19 incidence for 90 days post-Peak, but viral evolution and waning antibodies abrogate this protection thereafter.
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Mkhize, Nonhlanhla N, Bo Zhang, Caroline Brackett, Peter James Elyanu, Asa Tapley, Sufia Dadabhai, Jiani Hu, Bich TN Do, et al. (2025). Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV. Nature communications, 16(1). p. 8876. 10.1038/s41467-025-63948-4 Retrieved from https://hdl.handle.net/10161/33623.
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Scholars@Duke
Marcella Sarzotti-Kelsoe
Ongoing Applied Activities
•I direct a Global Quality Assurance Program, which I developed and pioneered here at Duke University, to oversee compliance with Good Clinical Laboratory Practice Guidelines in three HIV vaccine trial networks (CHAVI, CAVD, Duke HVTN, EQAPOL, Duke VTEU) involving domestic and international laboratory sites.
•I also direct a Global Proficiency Testing Program for laboratories testing for neutralizing antibody function in individuals infected with HIV or vaccinated against HIV. The Program was launched in 2009.
•I provide assistance and oversight for endpoint assay standardization, qualification and validation, as well as for the QSU of the GMP facility at DHVI, which will manufacture HIV vaccine products for first-in-man Phase I trials.
Past Basic Research
•Development of T cell responses in neonates.
•Neonatal T cell receptor Vβ repertoire diversity in the peripheral T cell pool.
•The role of heat shock protein, as a natural adjuvant, at eliciting innate and adaptive immune responses.
•Development of the T cell receptor repertoire in naïve, immunodeficient infants, given bone marrow or thymic transplantation.
•Thymic output, T cell diversity and T cell function in long-term human SCID chimeras.
•Telomere length in T cells from SCID chimeras.
Avi Kenny
Avi Kenny is an Assistant Professor in the Department of Biostatistics and Bioinformatics at Duke University, with a secondary appointment at the Duke Global Health Institute. He holds a PhD in biostatistics from the University of Washington, where he developed statistical methods for immune correlates analysis of vaccine clinical trial data. Prior to this, he worked for five years in Liberia as the Director of Research, Monitoring, and Evaluation at Last Mile Health. His current research interests include statistical methods to handle treatment effect heterogeneity in cluster randomized trials, survival analysis using machine learning tools, evaluation of global health programs, and data quality assurance in low-resource settings.
Guido Ferrari
The activities of the Ferrari Laboratory are based on both independent basic research and immune monitoring studies. The research revolves around three main areas of interest: class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity (ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation along with many other productive collaborations within and outside of Duke, the Ferrari Lab has expanded its focus of research to include the ontogeny of HIV-1 specific immune responses that work by eliminating HIV-1 infected cells and how these can be induced by AIDS vaccine candidates.
David Charles Montefiori
Dr. Montefiori is Professor and Director of the Laboratory for HIV-1 and COVID-19 Vaccine Research & Development in the Department of Surgery, Division of Surgical Sciences at Duke University Medical Center. His major research interests are viral immunology and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing antibodies.
Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory, including mechanisms of neutralization and escape, epitope diversity among the different genetic subtypes and geographic distributions of the virus, neutralizing epitopes, requirements to elicit protective neutralizing antibodies by vaccination, optimal combinations of neutralizing antibodies for immunoprophylaxis, and novel vaccine designs for HIV-1. Dr. Montefiori also directs large vaccine immune monitoring programs funded by the NIH and the Foundation that operate in compliance with Good Clinical Laboratory Practices and has served as a national and international resource for standardized assessments of neutralizing antibody responses in preclinical and clinical trials of candidate HIV vaccines since 1988.
At the onset of the COVID-19 pandemic he turned his attention to SARS-CoV-2, with a special interest in emerging variants and how they might impact transmission, vaccines and immunotherapeutics. His rapid response to emerging SARS-CoV-2 variants of concern provided some of the earliest evidence of the potential risk the variants pose to vaccines. In May 2020, his laboratory was recruited by the US Government to lead the national neutralizing antibody laboratory program for COVID-19 vaccines. His laboratory utilizes FDA approved validated assay criteria to facilitate regulatory approvals of COVID-19 vaccines.
He has published over 850 original research papers that have helped shape the scientific rationale for antibody-based vaccines.
Georgia Doris Tomaras
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor of Molecular Genetics and Microbiology and is a Fellow of the American Academy of Microbiology (AAM) and a Fellow of the American Association for the Advancement of Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology (CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her national and international leadership roles include: Executive Management Team (EMT) leader and mPI for the HIV Vaccine Trials Network (HVTN); Director of Lab Sciences (HVTN); and Chair of NIH Vaccine Research Center (VRC) Board of Scientific Counselors. Her prior leadership roles include serving as the Director of Research, Duke Human Vaccine Institute (DHVI); Director of the DHVI Training Program; Associate Director of DHVI Research; Co-Director of the Interdisciplinary Research Training Program in AIDS (IRTPA) Duke; Chair of the National Institutes of Health (NIH) AIDS Vaccine Research Subcommittee (AVRS), and Advisory Counsel member of the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID). Dr. Tomaras’ primary research focus is deciphering mechanisms of protective human immunity and identification of immune correlates of protection to further development of effective vaccines against infectious diseases.
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