DNA Ad5 vaccination with SIV epitopes induced epitope specific CD4 T cells but few subdominant epitope specific CD8 T cells
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.
Vojnov L, Bean AT, Peterson EJ, Chiuchiolo MJ, Sacha JB, Denes FS, Sandor M, Fuller DH, Fuller JT, Parks CL, McDermott AB, Wilson NA, Watkins DI
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