Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys

Nat Commun. 2017 Jun 5;8:15740. doi: 10.1038/ncomms15740.

Abstract

Previous studies have shown that DNA prime, Ad5 boost vaccines protect against neutralization-sensitive but not neutralization-resistant virus variants within the SIVsmE660 swarm. Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35/Ad26 vectors expressing SIVmac239 Gag/Pol/Env with or without an AS01B-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad/Env vaccines. In a single, high-dose challenge study, only the Ad/Env vaccine affords significant protection against acquisition of infection. Analysis of transmitted/founder (T/F) viruses from this study demonstrates that the Ad/Env vaccine blocks both neutralization-sensitive and neutralization-resistant SIVsmE660 variants in rhesus monkeys with restrictive TRIM5α alleles. These data demonstrate that the adjuvanted Env protein boost is critical for protecting against high-dose SIVsmE660 challenge and for blocking neutralization-resistant viruses within the SIVsmE660 swarm.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antibodies, Neutralizing / immunology
  • Female
  • Gene Products, env / genetics
  • Gene Products, env / immunology*
  • Immunity, Humoral
  • Immunization, Secondary
  • Macaca mulatta
  • Male
  • Neutralization Tests
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / pathogenicity*
  • Vaccines, DNA / immunology
  • Vaccines, DNA / pharmacology*
  • Viral Vaccines / immunology
  • Viral Vaccines / pharmacology*

Substances

  • Antibodies, Neutralizing
  • Gene Products, env
  • Vaccines, DNA
  • Viral Vaccines