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

Publication ,  Journal Article
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; Sawatzki, K ...
Published in: Science
August 14, 2015

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

August 14, 2015

Volume

349

Issue

6249

Start / End Page

aab1253

Location

United States

Related Subject Headings

  • Vaccines, DNA
  • Microbiota
  • Intestines
  • Immunologic Memory
  • Immunoglobulin Variable Region
  • Immunoglobulin Heavy Chains
  • Immunity
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
 

Citation

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Williams, W. B., Liao, H.-X., Moody, M. A., Kepler, T. B., Alam, S. M., Gao, F., … Haynes, B. F. (2015). HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science, 349(6249), aab1253. https://doi.org/10.1126/science.aab1253
Williams, Wilton B., Hua-Xin Liao, M Anthony Moody, Thomas B. Kepler, S Munir Alam, Feng Gao, Kevin Wiehe, et al. “HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies.Science 349, no. 6249 (August 14, 2015): aab1253. https://doi.org/10.1126/science.aab1253.
Williams WB, Liao H-X, Moody MA, Kepler TB, Alam SM, Gao F, et al. HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science. 2015 Aug 14;349(6249):aab1253.
Williams, Wilton B., et al. “HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies.Science, vol. 349, no. 6249, Aug. 2015, p. aab1253. Pubmed, doi:10.1126/science.aab1253.
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. HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science. 2015 Aug 14;349(6249):aab1253.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

August 14, 2015

Volume

349

Issue

6249

Start / End Page

aab1253

Location

United States

Related Subject Headings

  • Vaccines, DNA
  • Microbiota
  • Intestines
  • Immunologic Memory
  • Immunoglobulin Variable Region
  • Immunoglobulin Heavy Chains
  • Immunity
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41