e-Article
Leveraging antigenic seniority for maternal vaccination to prevent mother-to-child transmission of HIV-1
Document Type
article
Author
Ashley N. Nelson; Maria Dennis; Jesse F. Mangold; Katherine Li; Pooja T. Saha; Kenneth Cronin; Kaitlyn A. Cross; Amit Kumar; Riley J. Mangan; George M. Shaw; Katharine J. Bar; Barton Haynes; Anthony M. Moody; S. Munir Alam; Justin Pollara; Michael G. Hudgens; Koen K. A. Van Rompay; Kristina De Paris; Sallie R. Permar
Source
npj Vaccines, Vol 7, Iss 1, Pp 1-13 (2022)
Subject
Language
English
ISSN
2059-0105
Abstract
Abstract The development of a maternal HIV vaccine to synergize with current antiretroviral drug prophylaxis can overcome implementation challenges and further reduce mother-to-child transmission (MTCT) of HIV. Both the epitope-specificity and autologous neutralization capacity of maternal HIV envelope (Env)-specific antibodies have been implicated in decreased risk of MTCT of HIV. Our goal was to determine if heterologous HIV Env immunization of SHIV.C.CH505-infected, ART-suppressed female rhesus macaques (RMs) could boost autologous Env-specific antibodies. SHIV.C.CH505-infected female RMs (n = 12), began a daily ART regimen at 12 weeks post-infection (wpi), which was continued for 12 weeks. Starting 2 weeks after ART initiation, RMs received 3 monthly immunizations with HIV b.63521/1086.C gp120 or placebo (n = 6/group) vaccine with adjuvant STR8S-C. Compared to the placebo-immunized animals, Env-vaccinated, SHIV-infected RMs exhibited enhanced IgG binding, avidity, and ADCC responses against the vaccine immunogens and the autologous SHIV.C.CH505 Env. Notably, the Env-specific memory B cells elicited by heterologous vaccination were dominated by cells that recognized the SHIV.C.CH505 Env, the antigen of primary exposure. Thus, vaccination of SHIV-infected, ART-suppressed RMs with heterologous HIV Envs can augment multiple components of the antibody response against the Env antigen of primary exposure, suggesting antigenic seniority. Our results suggest that a universal maternal HIV vaccination regimen can be developed to leverage antigenic seniority in targeting the maternal autologous virus pool.