Passa al contenuto
Merck

HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.

JCI insight (2020-01-31)
David Easterhoff, Justin Pollara, Kan Luo, Benjamin Janus, Neelakshi Gohain, LaTonya D Williams, Matthew Zirui Tay, Anthony Monroe, Kristina Peachman, Misook Choe, Susie Min, Paolo Lusso, Peng Zhang, Eden P Go, Heather Desaire, Mattia Bonsignori, Kwan-Ki Hwang, Charles Beck, Matina Kakalis, Robert J O'Connell, Sandhya Vasan, Jerome H Kim, Nelson L Michael, Jean-Louis Excler, Merlin L Robb, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Kevin Wiehe, Kevin O Saunders, David C Montefiori, Georgia D Tomaras, M Anthony Moody, James Arthos, Mangala Rao, M Gordon Joyce, Gilad Ofek, Guido Ferrari, Barton F Haynes
ABSTRACT

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.

MATERIALI
N° Catalogo
Marchio
Descrizione del prodotto

Deepwell 96 well plate, polypropylene, sterile, pack of 24 ea