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


ABSTRACT: 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.

SUBMITTER: Silva de Castro I 

PROVIDER: S-EPMC7847973 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Silva de Castro Isabela I   Gorini Giacomo G   Mason Rosemarie R   Gorman Jason J   Bissa Massimiliano M   Rahman Mohammad A MA   Arakelyan Anush A   Kalisz Irene I   Whitney Stephen S   Becerra-Flores Manuel M   Ni Eric E   Peachman Kristina K   Trinh Hung V HV   Read Michael M   Liu Mei-Hue MH   Van Ryk Donald D   Paquin-Proulx Dominic D   Shubin Zhanna Z   Tuyishime Marina M   Peele Jennifer J   Ahmadi Mohammed S MS   Verardi Raffaello R   Hill Juliane J   Beddall Margaret M   Nguyen Richard R   Stamos James D JD   Fujikawa Dai D   Min Susie S   Schifanella Luca L   Vaccari Monica M   Galli Veronica V   Doster Melvin N MN   Liyanage Namal P M NPM   Sarkis Sarkis S   Caccuri Francesca F   LaBranche Celia C   Montefiori David C DC   Tomaras Georgia D GD   Shen Xiaoying X   Rosati Margherita M   Felber Barbara K BK   Pavlakis George N GN   Venzon David J DJ   Magnanelli William W   Breed Matthew M   Kramer Josh J   Keele Brandon F BF   Eller Michael A MA   Cicala Claudia C   Arthos James J   Ferrari Guido G   Margolis Leonid L   Robert-Guroff Marjorie M   Kwong Peter D PD   Roederer Mario M   Rao Mangala M   Cardozo Timothy J TJ   Franchini Genoveffa G  

iScience 20210109 2


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 α<sub>4</sub>β<sub>7</sub> 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  ...[more]

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