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.
Original language | English (US) |
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Article number | e00923-17 |
Journal | Journal of virology |
Volume | 91 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2017 |
Funding
Research reported in this publication was supported by the NIAID of the NIH and by the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID; grant number UM1-AI100645), NIH NIAID Duke University Center for AIDS Research (CFAR; P30-AI-64518), the Office of Research Infrastructure Programs/OD (P51OD011107) (to CNPRC), and the intramural research program of the Vaccine Research Center, NIAID, NIH.
Keywords
- Gp41
- HIV-1 envelope
- HIV-1 vaccine
- Microbiome
- Rhesus macaques
ASJC Scopus subject areas
- Microbiology
- Immunology
- Insect Science
- Virology