|Title||HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Easterhoff, D, Pollara, J, Luo, K, Janus, B, Gohain, N, Williams, LTD, Tay, MZirui, Monroe, A, Peachman, K, Choe, M, Min, S, Lusso, P, Zhang, P, Go, EP, Desaire, H, Bonsignori, M, Hwang, K-K, Beck, C, Kakalis, M, O'Connell, RJ, Vasan, S, Kim, JH, Michael, NL, Excler, J-L, Robb, ML, Rerks-Ngarm, S, Kaewkungwal, J, Pitisuttithum, P, Nitayaphan, S, Sinangil, F, Tartaglia, J, Phogat, S, Wiehe, K, Saunders, KO, Montefiori, DC, Tomaras, GD, M Moody, A, Arthos, J, Rao, M, M Joyce, G, Ofek, GA, Ferrari, G, Haynes, BF|
|Date Published||2020 01 30|
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.
|Alternate Journal||JCI Insight|