Abstract
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.
Original language | English (US) |
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Pages (from-to) | 7483-7490 |
Number of pages | 8 |
Journal | Vaccine |
Volume | 29 |
Issue number | 43 |
DOIs | |
State | Published - Oct 6 2011 |
Externally published | Yes |
Keywords
- CD4+ T cells
- CD8+ T cells
- DNA/Ad5 vaccination
- Subdominant epitopes
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases