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 α4β7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β 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 β 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. [Display omitted] •HIV vaccine candidate protects against SIVmac251 acquisition•V1 deleted envelope immunogens with V2 in α-helical conformation are protective•V2-specific ADCC as correlate of risk•Anti-V1 antibodies interfere with V2-specific ADCC Immunology; molecular structure; virology