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HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies.
- Source :
-
Science (New York, N.Y.) [Science] 2015 Aug 14; Vol. 349 (6249), pp. aab1253. Date of Electronic Publication: 2015 Jul 30. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015, American Association for the Advancement of Science.)
- Subjects :
- Adenoviridae
Antibodies, Monoclonal genetics
Antibodies, Monoclonal immunology
Antibody Formation
Cross Reactions
HIV Antibodies genetics
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp41 genetics
Humans
Immunity
Immunoglobulin Heavy Chains genetics
Immunoglobulin Heavy Chains immunology
Immunoglobulin Variable Region genetics
Immunoglobulin Variable Region immunology
Immunologic Memory
Intestines microbiology
AIDS Vaccines immunology
HIV Antibodies immunology
HIV Envelope Protein gp41 immunology
HIV-1 immunology
Microbiota immunology
Vaccines, DNA immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 349
- Issue :
- 6249
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 26229114
- Full Text :
- https://doi.org/10.1126/science.aab1253