Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response

• DOI: 10.1371/journal.ppat.1011359
• Publication Date: 2023-05-31T18:09:53Z
• Authors: LaTonya D. Williams; Xiaoying Shen; Sheetal S. Sawant; Siriwat Akapirat; Lindsay C. Dahora; Matthew Zirui Tay; Sherry Stanfield-...; Saintedym Wills; Derrick Goodman; DeAnna Tenney; Rachel L. Spreng; Lu Zhang; Nicole L. Yates; David C. Montefiori; Michael A. Eller; David Easterhoff; Thomas J. Hope; Supachai Rerks-Ngarm; Punnee Pittisutti...; Sorachai Nitayaphan; Jean-Louis Excler; Jerome H. Kim; Nelson L. Michael; Merlin L. Robb; Robert J. O’Connell; Nicos Karasavvas; Sandhya Vasan; Guido Ferrari; Georgia D. Tomaras
• Keywords: HIV vaccine; AIDS Vaccines

The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates decreased infection risk. New strategies to increase magnitude and durability protective immunity are critically needed. RV305 clinical trial evaluated immunological impact a follow-up boost HIV-1-uninfected RV144 recipients after 6–8 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 or ALVAC-HIV + gp120). Previous reports demonstrated that this elicited higher binding, antibody Fc function, cellular responses than primary regimen. However, canarypox viral vector in driving specificity, breadth, function is unknown. We performed analysis humoral determine different booster on epitope subclass, isotype, effector functions. Importantly, we observed ALVAC component directly contributed improved vaccine-elicited responses. Extended boosts increased circulating concentration coverage heterologous strains by V1V2-specific antibodies above estimated levels RV144. Antibody functions, specifically antibody-dependent cytotoxicity phagocytosis, were boosted was achieved V1V2 Env IgG3, correlate lower risk, not increased; plasma IgA (specifically IgA1), elevated. quality polyclonal response changed each immunization. Remarkably, immunogen induced post-second boost, indicating can be utilized selectively enhance These results reveal complex dynamic post-vaccination may require careful balancing achieve vaccinated population. Trial registration : (ClinicalTrials.gov number, NCT01435135 ). ClinicalTrials.gov Identifier: NCT00223080 .