iScience (Feb 2021)
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
Affiliations
- Isabela Silva de Castro
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Giacomo Gorini
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Rosemarie Mason
- ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Jason Gorman
- Structural Biology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Massimiliano Bissa
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Mohammad A. Rahman
- Immune Biology of Retroviral Infection Section, National Cancer Institute, Bethesda, MD 20892, USA
- Anush Arakelyan
- Section on Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
- Irene Kalisz
- Advanced Bioscience Laboratories, Rockville, MD 20850, USA
- Stephen Whitney
- Advanced Bioscience Laboratories, Rockville, MD 20850, USA
- Manuel Becerra-Flores
- New York University School of Medicine, NYU Langone Health, New York, NY 10016, USA
- Eric Ni
- New York University School of Medicine, NYU Langone Health, New York, NY 10016, USA
- Kristina Peachman
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Hung V. Trinh
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Michael Read
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Mei-Hue Liu
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Donald Van Ryk
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Dominic Paquin-Proulx
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Zhanna Shubin
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Marina Tuyishime
- Division of Surgical Sciences, Duke University School of Medicine, Durham, NC 27701, USA
- Jennifer Peele
- Division of Surgical Sciences, Duke University School of Medicine, Durham, NC 27701, USA
- Mohammed S. Ahmadi
- Structural Biology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Raffaello Verardi
- Structural Biology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Juliane Hill
- ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Margaret Beddall
- ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Richard Nguyen
- ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- James D. Stamos
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Dai Fujikawa
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Susie Min
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Luca Schifanella
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Monica Vaccari
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Veronica Galli
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Melvin N. Doster
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Namal P.M. Liyanage
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Sarkis Sarkis
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Francesca Caccuri
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Celia LaBranche
- Division of Surgical Sciences, Duke University School of Medicine, Durham, NC 27701, USA
- David C. Montefiori
- Division of Surgical Sciences, Duke University School of Medicine, Durham, NC 27701, USA
- Georgia D. Tomaras
- Duke Human Vaccine Institute, Duke University, Durham, NC 27701, USA
- Xiaoying Shen
- Duke Human Vaccine Institute, Duke University, Durham, NC 27701, USA
- Margherita Rosati
- Human Retrovirus Section, National Cancer Institute, Frederick, MD 21702, USA
- Barbara K. Felber
- Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, MD 21702, USA
- George N. Pavlakis
- Human Retrovirus Section, National Cancer Institute, Frederick, MD 21702, USA
- David J. Venzon
- Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- William Magnanelli
- AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21704, USA
- Matthew Breed
- AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21704, USA
- Josh Kramer
- AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21704, USA
- Brandon F. Keele
- AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21704, USA
- Michael A. Eller
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Claudia Cicala
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- James Arthos
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Guido Ferrari
- Division of Surgical Sciences, Duke University School of Medicine, Durham, NC 27701, USA
- Leonid Margolis
- Section on Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
- Marjorie Robert-Guroff
- Immune Biology of Retroviral Infection Section, National Cancer Institute, Bethesda, MD 20892, USA
- Peter D. Kwong
- Structural Biology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Mario Roederer
- ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Mangala Rao
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Timothy J. Cardozo
- New York University School of Medicine, NYU Langone Health, New York, NY 10016, USA; Corresponding author
- Genoveffa Franchini
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 2
p. 102047
Abstract
Summary: 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.
