Multigene DNA priming-boosting vaccines protect macaques from acute CD4+-T-cell depletion after simian-human immunodeficiency virus SHIV89.6P mucosal challenge

J Virol. 2003 Nov;77(21):11563-77. doi: 10.1128/jvi.77.21.11563-11577.2003.

Abstract

We evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus SHIV89.6P in Macaca nemestrina. Each regimen included gene gun delivery of a DNA vaccine expressing all SHIV89.6 genes plus Env gp160 of SHIV89.6P. Additional components were two recombinant vaccinia viruses, expressing SHIV89.6 Gag-Pol or Env gp160, and inactivated SHIV89.6 virus. We compared (i) DNA priming/DNA boosting, (ii) DNA priming/inactivated virus boosting, (iii) DNA priming/vaccinia virus boosting, and (iv) vaccinia virus priming/DNA boosting versus sham vaccines in groups of 6 macaques. Prechallenge antibody responses to Env and Gag were strongest in the groups that received vaccinia virus priming or boosting. Cellular immunity to SHIV89.6 peptides was measured by enzyme-linked immunospot assay; strong responses to Gag and Env were found in 9 of 12 vaccinia virus vaccinees and 1 of 6 DNA-primed/inactivated-virus-boosted animals. Vaccinated macaques were challenged intrarectally with 50 50% animal infectious doses of SHIV89.6P 3 weeks after the last immunization. All animals became infected. Five of six DNA-vaccinated and 5 of 6 DNA-primed/particle-boosted animals, as well as all 6 controls, experienced severe CD4(+)-T-cell loss in the first 3 weeks after infection. In contrast, DNA priming/vaccinia virus boosting and vaccinia virus priming/DNA boosting vaccines both protected animals from disease: 11 of 12 macaques had no loss of CD4(+) T cells or moderate declines. Virus loads in plasma at the set point were significantly lower in vaccinia virus-primed/DNA-boosted animals versus controls (P = 0.03). We conclude that multigene vaccines delivered by a combination of vaccinia virus and gene gun-delivered DNA were effective against SHIV89.6P viral challenge in M. nemestrina.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Viral / blood
  • Biolistics
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • HIV Envelope Protein gp160 / genetics
  • HIV Envelope Protein gp160 / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • Humans
  • Immunity, Cellular
  • Immunization
  • Immunization, Secondary*
  • Macaca nemestrina
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Substances

  • AIDS Vaccines
  • Antibodies, Viral
  • HIV Envelope Protein gp160
  • SAIDS Vaccines
  • Vaccines, DNA
  • Viral Proteins