DNA/Ad5 vaccination with SIV epitopes induced epitope-specific CD4⁺ T cells, but few subdominant epitope-specific CD8⁺ T cells

Vaccine. 2011 Oct 6;29(43):7483-90. doi: 10.1016/j.vaccine.2011.07.048. Epub 2011 Aug 10.


The goals of a T cell-based vaccine for HIV are to reduce viral peak and setpoint and prevent transmission. While it has been relatively straightforward to induce CD8(+) T cell responses against immunodominant T cell epitopes, it has been more difficult to broaden the vaccine-induced CD8(+) T cell response against subdominant T cell epitopes. Additionally, vaccine regimens to induce CD4(+) T cell responses have been studied only in limited settings. In this study, we sought to elicit CD8(+) T cells against subdominant epitopes and CD4(+) T cells using various novel and well-established vaccine strategies. We vaccinated three Mamu-A*01(+) animals with five Mamu-A*01-restricted subdominant SIV-specific CD8(+) T cell epitopes. All three vaccinated animals made high frequency responses against the Mamu-A*01-restricted Env TL9 epitope with one animal making a low frequency CD8(+) T cell response against the Pol LV10 epitope. We also induced SIV-specific CD4(+) T cells against several MHC class II DRBw*606-restricted epitopes. Electroporated DNA with pIL-12 followed by a rAd5 boost was the most immunogenic vaccine strategy. We induced responses against all three Mamu-DRB*w606-restricted CD4 epitopes in the vaccine after the DNA prime. Ad5 vaccination further boosted these responses. Although we successfully elicited several robust epitope-specific CD4(+) T cell responses, vaccination with subdominant MHC class I epitopes elicited few detectable CD8(+) T cell responses. Broadening the CD8(+) T cell response against subdominant MHC class I epitopes was, therefore, more difficult than we initially anticipated.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Epitopes, T-Lymphocyte / immunology
  • Histocompatibility Antigens Class I / immunology
  • Immunodominant Epitopes
  • Interleukin-12
  • Lymphocyte Activation*
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome / genetics
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Viral Proteins / immunology


  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Immunodominant Epitopes
  • Mamu-A 01 antigen
  • Vaccines, DNA
  • Viral Proteins
  • Interleukin-12