Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques

Virology. 2008 May 10;374(2):322-37. doi: 10.1016/j.virol.2007.12.037. Epub 2008 Feb 5.

Abstract

Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.6P model. All groups were primed with Ad-HIVenv89.6P, SIVgag239, and SIVnef239 recombinants. One group was not boosted, one received HIV89.6Pgp140DeltaCFI protein, and one a novel HIV-1 poly-peptide "peptomer". The HIV89.6Pgp140DeltaCFI protein in adjuvant strongly boosted Env-specific antibody and memory T cell responses in blood and tissue, resulting in significant reductions in acute and set point viremia. Macaques not boosted, showed a significant reduction in set point viremia, a full 32 weeks after the last Ad priming immunization. The HIV peptomer-boosted group showed a trend toward chronic viremia reduction, but was not protected.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology
  • Adenoviridae / genetics
  • Adenoviridae / physiology*
  • Animals
  • Genetic Vectors*
  • HIV Antibodies / blood
  • HIV Infections / prevention & control
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunization
  • Immunization, Secondary
  • Macaca mulatta
  • Male
  • Recombination, Genetic
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / pathogenicity
  • Simian Immunodeficiency Virus / radiation effects
  • T-Lymphocytes / immunology
  • Viremia / prevention & control*
  • Virus Replication
  • env Gene Products, Human Immunodeficiency Virus / administration & dosage
  • env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • Histocompatibility Antigens Class I
  • Mamu-A 01 antigen
  • SAIDS Vaccines
  • env Gene Products, Human Immunodeficiency Virus
  • gp140 envelope protein, Human immunodeficiency virus 1