| Literature DB >> 26229114 |
Wilton B Williams1, Hua-Xin Liao2, M Anthony Moody2, Thomas B Kepler3, S Munir Alam2, Feng Gao2, Kevin Wiehe2, Ashley M Trama2, Kathryn Jones2, Ruijun Zhang2, Hongshuo Song2, Dawn J Marshall2, John F Whitesides2, Kaitlin Sawatzki3, Axin Hua3, Pinghuang Liu2, Matthew Z Tay2, Kelly E Seaton2, Xiaoying Shen2, Andrew Foulger2, Krissey E Lloyd2, Robert Parks2, Justin Pollara2, Guido Ferrari2, Jae-Sung Yu2, Nathan Vandergrift2, David C Montefiori2, Magdalena E Sobieszczyk4, Scott Hammer4, Shelly Karuna5, Peter Gilbert6, Doug Grove6, Nicole Grunenberg5, M Juliana McElrath5, John R Mascola7, Richard A Koup7, Lawrence Corey5, Gary J Nabel7, Cecilia Morgan6, Gavin Churchyard8, Janine Maenza5, Michael Keefer9, Barney S Graham7, Lindsey R Baden10, Georgia D Tomaras2, Barton F Haynes1.
Abstract
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.Entities:
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Year: 2015 PMID： 26229114 PMCID： PMC4562404 DOI： 10.1126/science.aab1253
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728