Full-length HIV-1 immunogens induce greater magnitude and comparable breadth of T lymphocyte responses to conserved HIV-1 regions compared with conserved-region-only HIV-1 immunogens in rhesus monkeys

J Virol. 2012 Nov;86(21):11434-40. doi: 10.1128/JVI.01779-12. Epub 2012 Aug 15.

Abstract

A global HIV-1 vaccine will likely need to induce immune responses against conserved HIV-1 regions to contend with the profound genetic diversity of HIV-1. Here we evaluated the capacity of immunogens consisting of only highly conserved HIV-1 sequences that are aimed at focusing cellular immune responses on these potentially critical regions. We assessed in rhesus monkeys the breadth and magnitude of T lymphocyte responses elicited by adenovirus vectors expressing either full-length HIV-1 Gag/Pol/Env immunogens or concatenated immunogens consisting of only highly conserved HIV-1 sequences. Surprisingly, we found that the full-length immunogens induced comparable breadth (P = 1.0) and greater magnitude (P = 0.01) of CD8(+) T lymphocyte responses against conserved HIV-1 regions compared with the conserved-region-only immunogens. Moreover, the full-length immunogens induced a 5-fold increased total breadth of HIV-1-specific T lymphocyte responses compared with the conserved-region-only immunogens (P = 0.007). These results suggest that full-length HIV-1 immunogens elicit a substantially increased magnitude and breadth of cellular immune responses compared with conserved-region-only HIV-1 immunogens, including greater magnitude and comparable breadth of responses against conserved sequences.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Adenoviridae / genetics
  • Animals
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Drug Carriers
  • Genetic Vectors
  • HIV-1 / immunology*
  • Macaca mulatta
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • pol Gene Products, Human Immunodeficiency Virus / genetics
  • pol Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • Antigens, Viral
  • Drug Carriers
  • Vaccines, Synthetic
  • env Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • pol Gene Products, Human Immunodeficiency Virus