Reduced cell-associated DNA and improved viral control in macaques following passive transfer of a single anti-V2 monoclonal antibody and repeated simian/human immunodeficiency virus challenges

Ann J. Hessell, Mariya B. Shapiro, Rebecca Powell, Delphine C. Malherbe, Sean P. McBurney, Shilpi Pandey, Tracy Cheever, William F. Sutton, Christoph Kahl, Byung Park, Susan Zolla-Pazner, Nancy L. Haigwood

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

A high level of V1V2-specific IgG antibodies (Abs) in vaccinees' sera was the only independent variable that correlated with a reduced risk of human immunodeficiency virus (HIV) acquisition in the RV144 clinical trial. In contrast, IgG avidity, antibody neutralization, and antibody-dependent cellular cytotoxicity each failed as independent correlates of infection. Extended analyses of RV144 samples demonstrated the antiviral activities of V1V2-specific vaccine-induced antibodies. V2-specific antibodies have also been associated with protection from simian immunodeficiency virus (SIV), and the V2ispecific subset of human monoclonal antibodies (MAbs), while poor neutralizers, mediates Fc-dependent antiviral functions in vitro. The objective of this study was to determine the protective efficacy of a V2i-specific human MAb, 830A, against mucosal simian/ human immunodeficiency virus (SHIV) challenge. V2i MAb binding sites overlap the integrin binding site in the V2 region and are similar to the epitopes bound by antibodies associated with reduced HIV infection rates in RV144. Because the IgG3 subclass was a correlate of reduced infection rates in RV144, we compared passive protection by both IgG1 and IgG3 subclasses of V2i MAb 830A. This experiment represents the first in vivo test of the hypothesis emanating from RV144 and SIV studies that V2i Abs can reduce the risk of infection. The results show that passive transfer with a single V2i MAb, IgG1 830A, reduced plasma and peripheral blood mononuclear cell (PBMC) virus levels and decreased viral DNA in lymphoid tissues compared to controls, but too few animals remained uninfected to achieve significance in reducing the risk of infection. Based on these findings, we conclude that V2i antibodies can impede virus seeding following mucosal challenge, resulting in improved virus control.

Original languageEnglish (US)
Article numbere02198-17
JournalJournal of virology
Volume92
Issue number11
DOIs
StatePublished - Jun 1 2018

Keywords

  • Envelope protein
  • Gp120
  • HIV
  • Monoclonal antibody
  • Nonhuman primate models
  • Passive immunity
  • Passive transfer
  • V2 region

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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