Protective Efficacy of a Global HIV-1 Mosaic Vaccine Against Heterologous SHIV Challenges in Rhesus Monkeys

Cell. 2013 Oct 24;155(3):531-9. doi: 10.1016/j.cell.2013.09.061. Epub 2013 Oct 24.

Abstract

The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine. PAPERCLIP:

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibody Formation
  • Female
  • HIV Antigens / immunology
  • HIV-1*
  • Human Immunodeficiency Virus Proteins / immunology
  • Immunity, Cellular
  • Macaca mulatta
  • Male
  • Molecular Sequence Data
  • Specific Pathogen-Free Organisms

Substances

  • AIDS Vaccines
  • HIV Antigens
  • Human Immunodeficiency Virus Proteins

Associated data

  • GENBANK/KF042063