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.
Silva de Castro, I; Gorini, G; Mason, R; Gorman, J; Bissa, M; Rahman, MA; Arakelyan, A; Kalisz, I; Whitney, S; Becerra-Flores, M; Ni, E; Peachman, K; Trinh, HV; Read, M; Liu, M-H; Van Ryk, D; Paquin-Proulx, D; Shubin, Z; Tuyishime, M; Peele, J; Ahmadi, MS; Verardi, R; Hill, J; Beddall, M; Nguyen, R; Stamos, JD; Fujikawa, D; Min, S; Schifanella, L; Vaccari, M; Galli, V; Doster, MN; Liyanage, NPM; Sarkis, S; Caccuri, F; LaBranche, C; Montefiori, DC; Tomaras, GD; Shen, X; Rosati, M; Felber, BK; Pavlakis, GN; Venzon, DJ; Magnanelli, W; Breed, M; Kramer, J; Keele, BF; Eller, MA; Cicala, C; Arthos, J; Ferrari, G; Margolis, L; Robert-Guroff, M; Kwong, PD; Roederer, M; Rao, M; Cardozo, TJ; Franchini, G
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