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- Title
Leveraging antigenic seniority for maternal vaccination to prevent mother-to-child transmission of HIV-1.
- Authors
Nelson, Ashley N.; Dennis, Maria; Mangold, Jesse F.; Li, Katherine; Saha, Pooja T.; Cronin, Kenneth; Cross, Kaitlyn A.; Kumar, Amit; Mangan, Riley J.; Shaw, George M.; Bar, Katharine J.; Haynes, Barton; Moody, Anthony M.; Munir Alam, S.; Pollara, Justin; Hudgens, Michael G.; Van Rompay, Koen K. A.; De Paris, Kristina; Permar, Sallie R.
- 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.
- Subjects
MATERNALLY acquired immunity; AIDS vaccines; IMMUNOLOGIC memory; EMPLOYEE seniority; VACCINATION; HIV
- Publication
NPJ Vaccines, 2022, Vol 7, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-022-00505-w