Iris Castro, Teresa M. Giret, Diogo M. Magnani, Helen S. Maxwell, Oliver Umland, Jessica K. Perry, Jerilyn K. Pecotte, Kathleen M. Brasky, Glen N. Barber, Ronald C. Desrosiers, David I. Watkins

There are currently 5-10 million Human T-Lymphotropic Virus type 1 (HTLV-1)-infected people and many of these will develop severe complications resulting from this infection. A vaccine is urgently needed in HTLV-1-endemic areas. Many vaccines are best tested in non-human primate animal models. As a first step in designing an effective HTLV-1 vaccine, we defined the CD8+ and CD4+ T cell response against Simian T-Lymphotropic Virus type 1 (STLV-1)-a virus closely related to HTLV-1-in olive baboons (Papio anubis). Consistent with persistent antigenic exposure, we observed that STLV-1-specific CD8+ T cells displayed an effector memory phenotype and usually expressed CD107a, IFN-γ, and TNF-α. To assess the viral targets of the cellular immune response in STLV-1-infected animals, we used intracellular cytokine staining to detect responses against overlapping peptides covering the entire STLV-1 proteome. Our results show that, similar to humans, the baboon CD8+ T cell response narrowly targeted the Tax protein. Our findings suggest that the STLV-1-infected baboon model may recapitulate some of the important aspects of the human response against HTLV-1 and could be an important tool for the development of immune-based therapy and prophylaxis. HTLV-1 infection can lead to many different and often fatal conditions. A vaccine deployed in areas of high prevalence might reduce the incidence of HTLV-1-induced disease. Unfortunately, there are very few animal models of HTLV-1 infection useful for testing vaccine approaches. Here we describe cellular immune responses in baboons against a closely related virus, STLV-1. We show for the first time that the immune response against STLV-1 in naturally infected baboons is largely directed against the Tax protein. Similar findings in humans and the sequence similarity between the human and baboon viruses suggest that the STLV-1-infected baboon model might be useful for developing a vaccine against HTLV-1.