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


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.

SUBMITTER: Easterhoff D 

PROVIDER: S-EPMC7098725 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Easterhoff David D   Pollara Justin J   Luo Kan K   Janus Benjamin B   Gohain Neelakshi N   Williams LaTonya D LD   Tay Matthew Zirui MZ   Monroe Anthony A   Peachman Kristina K   Choe Misook M   Min Susie S   Lusso Paolo P   Zhang Peng P   Go Eden P EP   Desaire Heather H   Bonsignori Mattia M   Hwang Kwan-Ki KK   Beck Charles C   Kakalis Matina M   O'Connell Robert J RJ   Vasan Sandhya S   Kim Jerome H JH   Michael Nelson L NL   Excler Jean-Louis JL   Robb Merlin L ML   Rerks-Ngarm Supachai S   Kaewkungwal Jaranit J   Pitisuttithum Punnee P   Nitayaphan Sorachai S   Sinangil Faruk F   Tartaglia James J   Phogat Sanjay S   Wiehe Kevin K   Saunders Kevin O KO   Montefiori David C DC   Tomaras Georgia D GD   Moody M Anthony MA   Arthos James J   Rao Mangala M   Joyce M Gordon MG   Ofek Gilad G   Ferrari Guido G   Haynes Barton F BF  

JCI insight 20200130 2


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  ...[more]

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