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J Virol. 2017 Oct 13;91(21). pii: e00923-17. doi: 10.1128/JVI.00923-17. Print 2017 Nov 1.

HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques.

Author information

1
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
2
Department of Microbiology, Boston University, Boston, Massachusetts, USA.
3
Vaccine Research Center, NIH, Bethesda, Maryland, USA.
4
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
5
California National Primate Research Center, University of California, Davis, California, USA.
6
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA barton.haynes@dm.duke.edu.

Abstract

Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41-reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.IMPORTANCE Our results are critical to current work in the HIV-1 vaccine field evaluating the phenomenon of gp41 immunodominance induced by HIV-1 Env gp140 in RMs and humans. Our data demonstrate that RMs are an appropriate animal model to study this phenomenon and to determine the immunogenicity in new HIV-1 Env trimer vaccine designs. The demonstration of gp41 immunodominance in memory B cells of both adult and neonatal RMs indicated that early vaccination could not overcome gp41 dominant responses.

KEYWORDS:

HIV-1 envelope; HIV-1 vaccine; gp41; microbiome; rhesus macaques

PMID:
28794027
PMCID:
PMC5640856
DOI:
10.1128/JVI.00923-17
[Indexed for MEDLINE]
Free PMC Article

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