Computational analysis of antibody dynamics identifies recent HIV-1 infection.
Abstract
Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention
strategies. Current assays are limited by high false recent rates (FRRs) in certain
populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1
antibody response kinetics were harnessed to identify biomarkers for improved incidence
assays. We conducted retrospective analyses on circulating antibodies from known recent
and longstanding infections and evaluated binding and avidity measurements of Env
and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA,
and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant
function analysis identified an optimal set of measurements that were subsequently
evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included
clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140
IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215
day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and
3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype
and antigen interactions during infection enabled design of a promising HIV-1 recency
assay for improved cross-sectional incidence estimation.
Type
Journal articleSubject
CEPHIA groupHumans
HIV-1
HIV Infections
Immunoglobulin G
HIV Antibodies
HIV Antigens
Incidence
Retrospective Studies
Computational Biology
Antigen-Antibody Reactions
Antibody Affinity
Time Factors
Biomarkers
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https://hdl.handle.net/10161/22001Published Version (Please cite this version)
10.1172/jci.insight.94355Publication Info
Seaton, Kelly E; Vandergrift, Nathan A; Deal, Aaron W; Rountree, Wes; Bainbridge,
John; Grebe, Eduard; ... Tomaras, Georgia D (2017). Computational analysis of antibody dynamics identifies recent HIV-1 infection. JCI insight, 2(24). 10.1172/jci.insight.94355. Retrieved from https://hdl.handle.net/10161/22001.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
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. He has recently been
appointed to the Duke University Fuqua School of Business Health Sector Advisory Council.
Previously, he was an Associate Professor of Pathology, Laboratory M
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human
immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the
enabling technology to make preventive vaccines against these three major infectious
diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working
to determine why broadly neutralizing antibodies are rarely made in acute HIV infection
(AHI), currently a major obstacle in the de
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
Xiaoying Shen
Associate Professor in Surgery
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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