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 receptor. SIV vaccines engineered to delete V1 and favor an a-helix, rather than a β-sheet V2 conformation, enhanced 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 a 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, Isabela and Gorini, Giacomo and Mason, Rosemarie and Gorman, Jason and Bissa, Massimiliano and Rahman, Mohammad Arif and Arakelyan, Anush and Kalisz, Irene and Whitmey, Stephen and Becerra-Flores, Manuel and Ni, Eric and Peachman, Kristina and Trinh, Hung V. and Read, Michael and Liu, Mei-Hue and Van Ryk, Donald and Paquin-Proulx, Dominic and Shubin, Zhanna and Tuyishime, Marina and Peele, Jennifer and Ahmadi, Mohammed S. and Verardi, Raffaello and Hill, Juliane and Beddall, Margaret and Nguyen, R. and Stamos, James and Fujikawa, Dai and Min, Susie and Schifanella, Luca and Vaccari, Monica and Galli, Veronica and Doster, Melvin N. and Liyanage, Namal PM and Sarkis, Sarkis and Caccuri, Francesca and LaBranche, Celia and Montefiori, David C. and Tomaras, Georgia D. and Shen, Xiaoying and Rosati, Margherita and Felber, Barbara K. and Pavlakis, George N. and Venzon, David J. and Magnanelli, William and Breed, Matthew and Kramer, Josh and Keele, Brandon F. and Eller, Michael A. and Cicala, Claudia and Arthos, James and Ferrari, Guido and Margolis, Leonid and Robert-Guroff, Marjorie and Kwong, Peter D. and Roederer, Mario and Rao, Mangala and Cardozo, Timothy J. and Franchini, Genoveffa, Anti-V2 Antibodies Virus Vulnerability Revealed by Envelope V1 Deletion in HIV Vaccine Candidates. Available at SSRN: https://ssrn.com/abstract=3699153 or http://dx.doi.org/10.2139/ssrn.3699153
This version of the paper has not been formally peer reviewed.
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