Effect of pre-existing cytotoxic T lymphocytes on therapeutic vaccines

Eur J Immunol. 2000 Feb;30(2):671-7. doi: 10.1002/1521-4141(200002)30:2<671::AID-IMMU671>3.0.CO;2-H.


Therapeutic vaccines which aim to induce CD8(+) cytotoxic T lymphocyte (CTL) responses will often be required to perform in the presence of pre-existing CTL which recognize epitopes within the vaccine. Here we explore the ability of a viral vaccine vector presenting several co-dominant CTL epitopes to prime CTL responses in animals that have a pre-existing CTL response to one of the epitopes in the vaccine. The vaccine was usually capable of inducing multiple new responses, suggesting that immunodomination effects of pre-existing CTL may generally be minimal following vaccination. However, when large numbers of pre-existing CTL were present, a novel type of immune modulation was observed whereby (1) the vaccine failed to prime efficiently new CTL responses that were restricted by the same MHC gene as the pre-existing responses, and (2) vaccine-induced CTL responses restricted by other MHC genes were enhanced. These results may have implications for therapeutic multi-epitope vaccines for diseases like HIV and melanoma, which aim to broaden CTL responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Antigen Presentation
  • Cytotoxicity, Immunologic*
  • Epitopes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Vaccines / immunology*
  • Viral Vaccines / therapeutic use
  • Virus Diseases / immunology
  • Virus Diseases / prevention & control


  • Epitopes
  • Viral Vaccines