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

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

  2. Author Address

    NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.NCI, Immune Biol Retroviral Infect Sect, Bethesda, MD 20892 USA.Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, NIH, Bethesda, MD 20892 USA.Adv Biosci Labs, Rockville, MD 20850 USA.NYU, Sch Med, NYU Langone Hlth, New York, NY 10016 USA.Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA.Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.NIAID, Lab Immunoregulat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Duke Univ, Div Surg Sci, Sch Med, Durham, NC 27701 USA.Duke Univ, Duke Human Vaccine Inst, Durham, NC 27701 USA.NCI, Human Retrovirus Sect, Frederick, MD 21702 USA.NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA.NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21704 USA.NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    1. Year: 2021
    2. Date: Feb 19
  2. Journal: iScience
  3. Cell Press
    1. 24
    2. 2
  5. Type of Article: Article
  6. Article Number: ARTN 102047
  7. ISSN: 2589-0042
  1. 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 alpha(4)beta(7) integrin. SIV vaccines engineered to delete V1 and favor an alpha helix, rather than a beta 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 beta 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.

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External Sources

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  2. DOI: 10.1016/j.isci.2021.102047
  3. PMID: 33554060
  4. PMCID: PMC7847973
  5. View record in Web of Science®
  6. WOS: 000621266700022

Library Notes

  1. Fiscal Year: FY2020-2021
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