HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.
Abstract
Induction of broadly cross-reactive antiviral humoral responses with the capacity
to target globally diverse circulating strains is a key goal for HIV-1 immunogen design.
A major gap in the field is the identification of diverse HIV-1 envelope antigens
to evaluate vaccine regimens for binding antibody breadth. In this study, we define
unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability.
Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic
diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder
viruses with a tier 2 neutralization phenotype. Unique antigenicity was determined
by nonredundancy (Spearman correlation), and antigens were clustered using partitioning
around medoids (PAM) to identify antigen diversity. Cross-validation demonstrated
that the PAM method was better than selection by reactivity and random selection.
Analysis of vaccine-elicited V1V2 binding antibody in longitudinal samples from the
RV144 clinical trial revealed the striking heterogeneity among individual vaccinees
in maintaining durable responses. These data support the idea that a major goal for
vaccine development is to improve antibody levels, breadth, and durability at the
population level. Elucidating the level and durability of vaccine-elicited binding
antibody breadth needed for protection is critical for the development of a globally
efficacious HIV vaccine.IMPORTANCE The path toward an efficacious HIV-1 vaccine will
require characterization of vaccine-induced immunity that can recognize and target
the highly genetically diverse virus envelope glycoproteins. Antibodies that target
the envelope glycoproteins, including diverse sequences within the first and second
hypervariable regions (V1V2) of gp120, were identified as correlates of risk for the
one partially efficacious HIV-1 vaccine. To build upon this discovery, we experimentally
and computationally evaluated humoral responses to define envelope glycoproteins representative
of the antigenic diversity of HIV globally. These diverse envelope antigens distinguished
binding antibody breadth and durability among vaccine candidates, thus providing insights
for advancing the most promising HIV-1 vaccine candidates.
Type
Journal articleSubject
AnimalsMacaca mulatta
Humans
HIV-1
HIV Infections
HIV Envelope Protein gp120
AIDS Vaccines
HIV Antibodies
Genetic Variation
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https://hdl.handle.net/10161/17674Published Version (Please cite this version)
10.1128/JVI.01843-17Publication Info
Yates, Nicole L; deCamp, Allan C; Korber, Bette T; Liao, Hua-Xin; Irene, Carmela;
Pinter, Abraham; ... Tomaras, Georgia D (2018). HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses
and Durability among Vaccinees. Journal of virology, 92(8). 10.1128/JVI.01843-17. Retrieved from https://hdl.handle.net/10161/17674.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
S. Munir Alam
Professor in Medicine
Research Interests.
The Alam laboratory’s primary research is focused on understanding the biophysical
properties of antigen-antibody binding and the molecular events of early B cell activation
using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying
how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing
HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events
for their activation. In the lon
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
Hua-Xin Liao
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute.
Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made
major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus)
from Apodemus agraius using tissue culture in China. The successful identification
and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease,
and advancement of HFRS research towards prevention by de
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV 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,
Xiaoying Shen
Associate Professor in Surgery
Dr. Shen is an Associate Director and Deputy of the Laboratory for HIV and COVID-19
Vaccine Research & Development in the Department of Surgery, Division of Surgical
Sciences at Duke University Medical Center. Her research interest focuses on the humoral
immune response following virus infection or vaccination. During the past decade,
she has worked intensively on the specificity and breadth of binding antibody responses
against HIV. Dr. Shen’s team developed assays and
Georgia Doris Tomaras
Professor in Surgery
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 i
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