Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates

The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the alpha(4)beta(7) integrin. SIV vaccines engineered to delete V1 and favor an alpha helix, rather than a beta sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the beta sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

Automated summary

SIV vaccines engineered to delete V1 induce V2-specific ADCC, correlating with decreased risk of SIV acquisition, while removal of V1 from HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites.