Viral reservoir is suppressed but not eliminated by CD8 vaccine specific lymphocytes

Vaccine. 2010 Feb 23;28(8):1924-31. doi: 10.1016/j.vaccine.2009.10.100.

Abstract

It has long been postulated that while CD8 lymphocytes are capable of suppressing human immunodeficiency virus (HIV)-1 replication it is unlikely that the viral reservoirs once formed can be cleared. Our previous studies demonstrate that co-immunizing cynomologous macaques with a simian/human immunodeficiency virus (SHIV) DNA-based vaccines induces a strong cellular immune response that is able to suppress viral replication. We further demonstrated that interleukin (IL)-12 could significantly enhance the vaccine specific CD8 lymphocyte response. In this manuscript cynomologous macaques were vaccinated with a SHIV DNA-based vaccine co-delivered with IL-12. The macaques were then challenged with SHIV89.6p. Two years post-immunization and viral challenge we transiently depleted CD8(+) T cells. Plasma viral load increased, demonstrating the central role of CD8(+) T cells in viral suppression yet an inability to clear the viral reservoirs. Furthermore, in the data presented here, we found a higher number of IFN-gamma producing vaccine specific cells did not enhance suppression of viral replication.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Gene Products, gag / immunology
  • Immunity, Cellular
  • Immunologic Memory
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology*
  • Macaca
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / physiology
  • Vaccines, DNA / immunology*
  • Viral Load
  • Virus Replication

Substances

  • Gene Products, gag
  • SAIDS Vaccines
  • Vaccines, DNA
  • Interleukin-12
  • Interferon-gamma