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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
iScience | 2021

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.

Pubmed ID: 33554060 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007392
  • Agency: NIDA NIH HHS, United States
    Id: DP1 DA036478
  • Agency: CCR NIH HHS, United States
    Id: HHSN261200800001C
  • Agency: NCI NIH HHS, United States
    Id: HHSN261200800001E
  • Agency: NIH HHS, United States
    Id: P51 OD011104
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI084119

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Tulane National Primate Research Center (tool)

RRID:SCR_008167

Center focused on understanding human health problems, including infectious diseases that require the use of nonhuman primates to develop diagnostics, therapeutics and preventive strategies. Primary research interests include developing vaccines, treatments and diagnostic tools for infectious diseases such as AIDS, tuberculosis, CMV, COVID-19, Lyme disease, and malaria. TNPRC has both biosafety level 2 and biosafety level 3 laboratories facilities to accommodate various research needs, and is the only National Primate Research Center with Regional Biosafety Laboratory.

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