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

• DOI: 10.1016/j.isci.2021.102047
• Publication Date: 2021-01-12T22:37:41Z
• Authors: Isabela Silva de ...; Giacomo Gorini; Rosemarie Mason; Jason Gorman; Massimiliano Bissa; Mohammad A. Rahman; Anush Arakelyan; Irene Kalisz; Stephen Whitney; Manuel Becerra-Fl...; Eric Ni; Kristina Peachman; Hung V. Trinh; Michael Read; Mei-Hue Liu; Donald Van Ryk; Dominic Paquin-Pr...; Zhanna Shubin; Marina Tuyishime; Jennifer Peele; Mohammed S. Ahmadi; Raffaello Verardi; Juliane Hill; Margaret Beddall; Richard Nguyen; James D. Stamos; Dai Fujikawa; Susie Min; Luca Schifanella; Monica Vaccari; Veronica Galli; Melvin N. Doster; Namal P.M. Liyanage; Sarkis Sarkis; Francesca Caccuri; Celia LaBranche; David C. Montefiori; Georgia D. Tomaras; Xiaoying Shen; Margherita Rosati; Barbara K. Felber; George N. Pavlakis; David J. Venzon; William Magnanelli; Matthew Breed; Josh Kramer; Brandon F. Keele; Michael A. Eller; Claudia Cicala; James Arthos; Guido Ferrari; Leonid Margolis; Marjorie Robert-G...; Peter D. Kwong; Mario Roederer; Mangala Rao; Timothy J. Cardozo; Genoveffa Franchini
• Keywords: Envelope (radar); Vulnerability

The efficacy of ALVAC-based HIV and SIV vaccines in humans macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity reverse their ability block V2 peptide interaction the α4β7 integrin. engineered delete V1 favor an α helix, rather than a β sheet conformation, induced V2-specific ADCC correlating decreased risk acquisition. Removal from HIV-1 clade A/E A244 resulted binding recognizing conformation. Thus, deletion immunogens may improve antibody responses virus vulnerability sites increase vaccine candidates.