Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses

Virology. 2006 Sep 15;353(1):83-98. doi: 10.1016/j.virol.2006.05.012. Epub 2006 Jun 30.


Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies. Decreased viremia compared to naïve controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts < or =200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIV(mac251) challenge, was associated with durable protection against re-challenge.

Publication types

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

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology
  • Administration, Rectal
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Immunity, Cellular
  • Immunization, Secondary
  • Macaca mulatta
  • RNA, Viral / analysis
  • Recombinant Fusion Proteins / immunology
  • SAIDS Vaccines / administration & dosage*
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / isolation & purification
  • Time Factors
  • Vaccination
  • Vaccines, Synthetic / administration & dosage
  • Viremia
  • Virus Replication


  • RNA, Viral
  • Recombinant Fusion Proteins
  • SAIDS Vaccines
  • Vaccines, Synthetic