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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Williams, WB; Liao, H-X; Moody, MA; Kepler, TB; Alam, SM; Gao, F; Wiehe, K; Trama, AM; Jones, K; Zhang, R; Song, H; Marshall, DJ; Whitesides, JF; Sawatzki, K; Hua, A; Liu, P; Tay, MZ; Seaton, KE; Shen, X; Foulger, A; Lloyd, KE; Parks, R; Pollara, J; Ferrari, G; Yu, J-S; Vandergrift, N; Montefiori, DC; Sobieszczyk, ME; Hammer, S; Karuna, S; Gilbert, P; Grove, D; Grunenberg, N; McElrath, MJ; Mascola, JR; Koup, RA; Corey, L; Nabel, GJ; Morgan, C; Churchyard, G; Maenza, J; Keefer, M; Graham, BS; Baden, LR; Tomaras, GD; Haynes, BF

Published Date

  • August 14, 2015

Published In

Volume / Issue

  • 349 / 6249

Start / End Page

  • aab1253 -

PubMed ID

  • 26229114

Pubmed Central ID

  • 26229114

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aab1253

Language

  • eng

Conference Location

  • United States