Induction of HIV-1-specific antibody-mediated effector functions by native-like envelope trimers in humans

A protective vaccine is urgently needed to curb the ongoing global HIV-1 epidemic. There is increased interest to develop a vaccine able to induce both neutralizing antibodies and antibody-mediated effector functions for additional efficacy. We investigated the ability of a group M consensus envelope glycoprotein (Env) trimer vaccine ConM SOSIP.v7 to induce antibodies that mediate effector functions in preclinical and clinical studies. We found that the ConM SOSIP.v7 protein immunogen in combination with MPLA adjuvant induced diverse antibody-mediated effector functions in human volunteers participating in a phase 1 trial. Moreover, the functional antibody response was higher in female compared to male participants. The same immunogen induced similar antibody-mediated effector functions in preclinical studies using rabbits and non-human primates. In these preclinical models, we demonstrated that alterations in the vaccine regimen, including immunization route and adjuvant, could modulate vaccine immunogenicity and lead to functionally different antibody responses. Specifically, we observed that intramuscular immunization led to more functional antibody responses compared to subcutaneous vaccine administration, and that the MPLA liposomes and squalene emulsion adjuvants induced functionally different antibody responses. In conclusion, this study shows that HIV-1 native-like Env trimers are able to elicit antibody-mediated effector functions in humans and that preclinical studies had predictive value. Furthermore, the preclinical studies revealed that different vaccine formulations and administration routes yield qualitatively different antibody-mediated effector functions. Our findings should guide interpretation of preclinical HIV-1 vaccine studies and can inform the design of HIV-1 vaccine regimens aimed at inducing antibody-mediated effector functions in addition to neutralization capacity.