Abstract
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 human immunodeficiency virus, cytomegalovirus, and hepatitis C virus. Currently, various 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, the type and homing properties of the memory T cell subsets, and 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.
Highlights
Our bodies are persistently exposed to various pathogens present in the environment
We review determinants and mechanistic factors of effective T cell populations implicated in the vaccine efficacy against chronic viral infections, and discuss how this knowledge can be utilized to maximize the possibility of creating effective vaccine platforms for persistent viral infections
The latter approach incorporated a combination of subdominant and dominant epitopes of rhesus macaques simian immunodeficiency virus (SIV) in prime-boost vaccination schedules. In parallel with these findings, the efficacy of synthetic long peptide (SLP)-based vaccines to protect against mouse cytomegalovirus (MCMV) was significantly improved by combinations of SLPs that increased the breadth of the antigen-specific T cell response [5]
Summary
Our bodies are persistently exposed to various pathogens present in the environment. The immune system is fortified with physical barriers and with diverse immune cell populations that play an integral role in protection against disease. Long-term immune responses are mediated by antigenspecific lymphocytes and antibodies that are formed upon pathogen entry. Potent antibody inducing vaccines against virally induced diseases are available. They fail to provide long-term efficacy and protection against a number of chronic viral infections. Despite various promising vaccines that are capable of stimulating robust T cell responses, the critical factors of T cell-mediated immune protection against these chronic infections have not been clearly defined. Elucidating the mechanisms through which antigen-specific T cell populations mediate long-term protection against viruses at body surfaces and (lymphoid) tissues remains an important goal, and will facilitate the development of more effective and safe prophylactic T cell-eliciting vaccines. We review determinants and mechanistic factors of effective T cell populations implicated in the vaccine efficacy against chronic viral infections, and discuss how this knowledge can be utilized to maximize the possibility of creating effective vaccine platforms for persistent viral infections
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