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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Silva de Castro, I; Gorini, G; Mason, R; Gorman, J; Bissa, M; Rahman, MA; Arakelyan, A; Kalisz, I; Whitney, S; Becerra-Flores, M; Ni, E; Peachman, K; Trinh, HV; Read, M; Liu, M-H; Van Ryk, D; Paquin-Proulx, D; Shubin, Z; Tuyishime, M; Peele, J; Ahmadi, MS; Verardi, R; Hill, J; Beddall, M; Nguyen, R; Stamos, JD; Fujikawa, D; Min, S; Schifanella, L; Vaccari, M; Galli, V; Doster, MN; Liyanage, NPM; Sarkis, S; Caccuri, F; LaBranche, C; Montefiori, DC; Tomaras, GD; Shen, X; Rosati, M; Felber, BK; Pavlakis, GN; Venzon, DJ; Magnanelli, W; Breed, M; Kramer, J; Keele, BF; Eller, MA; Cicala, C; Arthos, J; Ferrari, G; Margolis, L; Robert-Guroff, M; Kwong, PD; Roederer, M; Rao, M; Cardozo, TJ; Franchini, G

Published Date

  • February 19, 2021

Published In

Volume / Issue

  • 24 / 2

Start / End Page

  • 102047 -

PubMed ID

  • 33554060

Pubmed Central ID

  • PMC7847973

Electronic International Standard Serial Number (EISSN)

  • 2589-0042

Digital Object Identifier (DOI)

  • 10.1016/j.isci.2021.102047

Language

  • eng

Conference Location

  • United States