Substantial envelope-specific CD8 T-cell immunity fails to control SIV disease.
It is unknown which HIV proteins to target by vaccination in order to generate the most effective CD8 T-cell immunity. We recently immunized SIV(mac251)-infected pigtail macaques with Gag peptides or a cocktail of peptides spanning all SIV proteins, including SIV Env. High-level SIV Env-specific CD8 T-cell responses were generated and 7 novel Env-specific CD8 T-cell epitopes in 10 animals were mapped. Env-specific CD8 T-cell responses were significantly inferior to Gag-specific responses, and no better than unvaccinated control animals, in the control of SIV replication and prevention of disease. Escape mutations emerged within several Env-specific CTL epitopes, suggesting at least some pressure imparted by the Env CTL responses, but this did not correlate with significantly reduced SIV replication. We conclude Env-specific CTL may not be the most effective response to induce by vaccination.
Peut
Viv
V
Department of Microbiology and Immunology, University of Melbourne, Parkville Victoria, Australia.
Kent
Stephen J
SJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D008251:Macaca; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017211:Treatment Failure; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000939:Epitopes; D015683:Gene Products, gag; D014759:Viral Envelope Proteins; D014765:Viral Vaccines