Publication Date:
2015-08-01
Description:
An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562404/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Wilton B -- Liao, Hua-Xin -- Moody, M Anthony -- Kepler, Thomas B -- Alam, S Munir -- Gao, Feng -- Wiehe, Kevin -- Trama, Ashley M -- Jones, Kathryn -- Zhang, Ruijun -- Song, Hongshuo -- Marshall, Dawn J -- Whitesides, John F -- Sawatzki, Kaitlin -- Hua, Axin -- Liu, Pinghuang -- Tay, Matthew Z -- Seaton, Kelly E -- Shen, Xiaoying -- Foulger, Andrew -- Lloyd, Krissey E -- Parks, Robert -- Pollara, Justin -- Ferrari, Guido -- Yu, Jae-Sung -- Vandergrift, Nathan -- Montefiori, David C -- Sobieszczyk, Magdalena E -- Hammer, Scott -- Karuna, Shelly -- Gilbert, Peter -- Grove, Doug -- Grunenberg, Nicole -- McElrath, M Juliana -- Mascola, John R -- Koup, Richard A -- Corey, Lawrence -- Nabel, Gary J -- Morgan, Cecilia -- Churchyard, Gavin -- Maenza, Janine -- Keefer, Michael -- Graham, Barney S -- Baden, Lindsey R -- Tomaras, Georgia D -- Haynes, Barton F -- P30 AI064518/AI/NIAID NIH HHS/ -- P30-AI-64518/AI/NIAID NIH HHS/ -- U01 AI069412/AI/NIAID NIH HHS/ -- UM1 AI068614/AI/NIAID NIH HHS/ -- UM1 AI068618/AI/NIAID NIH HHS/ -- UM1 AI068635/AI/NIAID NIH HHS/ -- UM1 AI069412/AI/NIAID NIH HHS/ -- UM1 AI069470/AI/NIAID NIH HHS/ -- UM1 AI069481/AI/NIAID NIH HHS/ -- UM1 AI069511/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1AI068618/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):aab1253. doi: 10.1126/science.aab1253. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu wilton.williams@duke.edu. ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. ; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA. ; Department of Medicine, Columbia University Medical Center, New York, NY, USA. ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; The Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; The Aurum Institute, Johannesburg, South Africa. ; University of Rochester School of Medicine, Rochester, NY, USA. ; Brigham and Women's Hospital, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229114" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/*immunology
;
Adenoviridae
;
Antibodies, Monoclonal/genetics/immunology
;
Antibody Formation
;
Cross Reactions
;
HIV Antibodies/genetics/*immunology
;
HIV Envelope Protein gp120/immunology
;
HIV Envelope Protein gp41/genetics/*immunology
;
HIV-1/*immunology
;
Humans
;
Immunity
;
Immunoglobulin Heavy Chains/genetics/immunology
;
Immunoglobulin Variable Region/genetics/immunology
;
Immunologic Memory
;
Intestines/microbiology
;
Microbiota/*immunology
;
Vaccines, DNA/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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