Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge

Nat Commun. 2017 Jun 8;8:15711. doi: 10.1038/ncomms15711.

Abstract

The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian-human immunodeficiency virus (SHIV) challenge. Systems serology of the antibody responses identifies plasma antibody binding to HIV-infected cells, peak ADCC antibody titres, NK cell-mediated ADCC and antibody-mediated activation of MIP-1β in NK cells as the four immunological parameters that best predict decreased infection risk that are improved by the pentavalent vaccine. Thus inclusion of additional gp120 immunogens to a pox-prime/protein boost regimen can augment antibody responses and enhance protection from a SHIV challenge in rhesus macaques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Complement System Proteins / immunology
  • Epitopes / immunology
  • Female
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Leukocytes, Mononuclear / cytology
  • Macaca mulatta
  • Male
  • Mutation
  • Neutralization Tests
  • Phagocytosis
  • Phylogeny
  • Predictive Value of Tests
  • Protein Binding
  • Recombinant Proteins / immunology
  • Regression Analysis
  • Simian Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Recombinant Proteins
  • Complement System Proteins