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

Isabela Silva de Castro; Giacomo Gorini; Rosemarie Mason; Jason Gorman; Massimiliano Bissa; Mohammad A Rahman; Anush Arakelyan; Irene Kalisz; Stephen Whitney; Manuel Becerra-Flores; Eric Ni; Kristina Peachman; Hung V Trinh; Michael Read; Mei-Hue Liu; Donald Van Ryk; Dominic Paquin-Proulx; 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-Guroff; Peter D Kwong; Mario Roederer; Mangala Rao; Timothy J Cardozo; Genoveffa Franchini

doi:10.1016/j.isci.2021.102047

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

iScience. 2021 Jan 9;24(2):102047. doi: 10.1016/j.isci.2021.102047. eCollection 2021 Feb 19.

Authors

Isabela Silva de Castro¹, Giacomo Gorini¹, Rosemarie Mason², Jason Gorman³, Massimiliano Bissa¹, Mohammad A Rahman⁴, Anush Arakelyan⁵, Irene Kalisz⁶, Stephen Whitney⁶, Manuel Becerra-Flores⁷, Eric Ni⁷, Kristina Peachman^{8

9}, Hung V Trinh^{8

9}, Michael Read⁹, Mei-Hue Liu¹⁰, Donald Van Ryk¹⁰, Dominic Paquin-Proulx^{8

9}, Zhanna Shubin^{8

9}, Marina Tuyishime¹¹, Jennifer Peele¹¹, Mohammed S Ahmadi³, Raffaello Verardi³, Juliane Hill², Margaret Beddall², Richard Nguyen², James D Stamos¹, Dai Fujikawa¹, Susie Min¹⁰, Luca Schifanella¹, Monica Vaccari¹, Veronica Galli¹, Melvin N Doster¹, Namal P M Liyanage¹, Sarkis Sarkis¹, Francesca Caccuri¹, Celia LaBranche¹¹, David C Montefiori¹¹, Georgia D Tomaras¹², Xiaoying Shen¹², Margherita Rosati¹³, Barbara K Felber¹⁴, George N Pavlakis¹³, David J Venzon¹⁵, William Magnanelli¹⁶, Matthew Breed¹⁶, Josh Kramer¹⁶, Brandon F Keele¹⁶, Michael A Eller^{8

9}, Claudia Cicala¹⁰, James Arthos¹⁰, Guido Ferrari¹¹, Leonid Margolis⁵, Marjorie Robert-Guroff⁴, Peter D Kwong³, Mario Roederer², Mangala Rao⁹, Timothy J Cardozo⁷, Genoveffa Franchini¹

Affiliations

¹ Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA.
² ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³ Structural Biology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Immune Biology of Retroviral Infection Section, National Cancer Institute, Bethesda, MD 20892, USA.
⁵ Section on Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Advanced Bioscience Laboratories, Rockville, MD 20850, USA.
⁷ New York University School of Medicine, NYU Langone Health, New York, NY 10016, USA.
⁸ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
⁹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
¹⁰ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹ Division of Surgical Sciences, Duke University School of Medicine, Durham, NC 27701, USA.
¹² Duke Human Vaccine Institute, Duke University, Durham, NC 27701, USA.
¹³ Human Retrovirus Section, National Cancer Institute, Frederick, MD 21702, USA.
¹⁴ Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, MD 21702, USA.
¹⁵ Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁶ AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21704, USA.

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.

Keywords: Immunology; molecular structure; virology.

Abstract

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