Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies

Wilton B. Williams, Hua Xin Liao, M. Anthony Moody, Thomas B. Kepler, S. Munir Alam, Feng Gao, Kevin Wiehe, Ashley M. Trama, Kathryn Jones, Ruijun Zhang, Hongshuo Song, Dawn J. Marshall, John F. Whitesides, Kaitlin Sawatzki, Axin Hua, Pinghuang Liu, Matthew Z. Tay, Kelly E. Seaton, Xiaoying Shen, Andrew FoulgerKrissey E. Lloyd, Robert Parks, Justin Pollara, Guido Ferrari, Jae Sung Yu, Nathan Vandergrift, David C. Montefiori, Magdalena E. Sobieszczyk, Scott Hammer, Shelly Karuna, Peter Gilbert, Doug Grove, Nicole Grunenberg, M. Juliana McElrath, John R. Mascola, Richard A. Koup, Lawrence Corey, Gary J. Nabel, Cecilia Morgan, Gavin Churchyard, Janine Maenza, Michael Keefer, Barney S. Graham, Lindsey R. Baden, Georgia D. Tomaras, Barton F. Haynes

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numberaab1253
JournalScience
Volume349
Issue number6249
DOIs
StatePublished - Aug 14 2015
Externally publishedYes

ASJC Scopus subject areas

  • General

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