Highly effective control of an AIDS virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus Ankara vaccine vectors in a single-boost protocol

J Virol. 2004 Apr;78(8):3930-40. doi: 10.1128/jvi.78.8.3930-3940.2004.

Abstract

Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect rhesus macaques from AIDS after challenge with the highly pathogenic SHIV 89.6P (23). In the present study, we compared the effectiveness of a single prime-boost protocol consisting of VSV vectors expressing SHIV Env, Gag, and Pol proteins to that of a protocol consisting of a VSV vector prime followed with a single boost with modified vaccinia virus Ankara (MVA) expressing the same SHIV proteins. After challenge with SHIV 89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2 x 10(6) copies/ml (a level significantly lower than that seen with VSV-boosted animals and lower than those reported for other vaccine studies employing the same challenge). MVA-boosted animals have shown excellent preservation of CD4(+) T cells, while two of four VSV-boosted animals have shown significant loss of CD4(+) T cells. The improved protection in MVA-boosted animals correlates with trends toward stronger prechallenge CD8(+)-T-cell responses to SHIV antigens and stronger postchallenge SHIV-neutralizing antibody production.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / genetics
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / prevention & control
  • Animals
  • Base Sequence
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • DNA, Recombinant / genetics
  • Genetic Vectors
  • HIV / genetics
  • HIV / isolation & purification
  • HIV Antibodies / biosynthesis
  • Immunization, Secondary
  • Macaca mulatta
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / genetics
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / isolation & purification
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / immunology

Substances

  • AIDS Vaccines
  • DNA, Recombinant
  • HIV Antibodies
  • SAIDS Vaccines
  • Vaccines, Synthetic