Features of Effective T Cell-Inducing Vaccines against Chronic Viral Infections

For many years the focus of prophylactic vaccines was to elicit neutralizing antibodies but it has become increasingly evident that T cell-mediated immunity plays a central role in controlling persistent viral infections such as with HIV, CMV, and HCV. Currently, a variety of promising prophylactic vaccines, capable of inducing substantial vaccine-specific T cell responses, are investigated in preclinical and clinical studies. There is compelling evidence that protection by T cells is related to the magnitude and breadth of the T cell response, to the type and homing properties of the memory T cell subsets, and to their cytokine polyfunctionality and metabolic fitness. In this review, we evaluated these key factors that determine the qualitative and quantitative properties of CD4+ and CD8+ T cell responses in the context of chronic viral disease and prophylactic vaccine development. Elucidation of the mechanisms underlying T cell-mediated protection against chronic viral pathogens will facilitate the development of more potent, durable and safe prophylactic T cell-based vaccines.