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Computational analysis of antibody dynamics identifies recent HIV-1 infection.

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Date
2017-12-21
Authors
Seaton, Kelly E
Vandergrift, Nathan A
Deal, Aaron W
Rountree, Wes
Bainbridge, John
Grebe, Eduard
Anderson, David A
Sawant, Sheetal
Shen, Xiaoying
Yates, Nicole L
Denny, Thomas N
Liao, Hua-Xin
Haynes, Barton F
Robb, Merlin L
Parkin, Neil
Santos, Breno R
Garrett, Nigel
Price, Matthew A
Naniche, Denise
Duerr, Ann C
CEPHIA group
Keating, Sheila
Hampton, Dylan
Facente, Shelley
Marson, Kara
Welte, Alex
Pilcher, Christopher D
Cohen, Myron S
Tomaras, Georgia D
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(29 total)
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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 article
Subject
CEPHIA group
Humans
HIV-1
HIV Infections
Immunoglobulin G
HIV Antibodies
HIV Antigens
Incidence
Retrospective Studies
Computational Biology
Antigen-Antibody Reactions
Antibody Affinity
Time Factors
Biomarkers
Permalink
https://hdl.handle.net/10161/22001
Published Version (Please cite this version)
10.1172/jci.insight.94355
Publication 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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Scholars@Duke

Denny

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
Haynes

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
Liao

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
Shen

Xiaoying Shen

Associate Professor in Surgery
Tomaras

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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