1区 · 医学
ArticleOA
作者: Kim, Jerome H ; Ofek, Gilad ; Excler, Jean-Louis ; Michael, Nelson L ; Zhang, Peng ; Wiehe, Kevin ; Choe, Misook ; Lusso, Paolo ; Pitisuttithum, Punnee ; Joyce, M Gordon ; Rerks-Ngarm, Supachai ; Min, Susie ; Ferrari, Guido ; Beck, Charles ; Peachman, Kristina ; Easterhoff, David ; Williams, LaTonya D ; Tartaglia, James ; Arthos, James ; Nitayaphan, Sorachai ; Tay, Matthew Zirui ; Janus, Benjamin ; Vasan, Sandhya ; Robb, Merlin L ; Haynes, Barton F ; Monroe, Anthony ; Phogat, Sanjay ; Moody, M Anthony ; Montefiori, David C ; Kakalis, Matina ; O'Connell, Robert J ; Sinangil, Faruk ; Gohain, Neelakshi ; Luo, Kan ; Saunders, Kevin O ; Rao, Mangala ; Tomaras, Georgia D ; Hwang, Kwan-Ki ; Go, Eden P ; Bonsignori, Mattia ; Desaire, Heather ; Pollara, Justin ; Kaewkungwal, Jaranit
In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.