Induction of Memory T Cells by Mimicking Natural Course of Infection

Abstract

Inducing robust and sustained T cell responses is necessary for therapeutic intervention of most infectious diseases. Unfortunately, many current subunit vaccine regimens fail to induce substantial cellular immunity. Potent cellular responses are an absolute necessity when it comes to achieving a state of complete protection and durable immunological memory in host systems. Vaccine invention and development has its roots lying under the concept of natural infection induced memory. Thus, mimicking infection can represent a good road map for guiding the development of novel subunit vaccine regimens. It has been noted that often responses to vaccination differ from those induced by infectious challenge, naturally. The failure of vaccines to a greater extent could be correlated to an incomplete understanding of the signals and cell types that operate at different stages of the immune response to influence the quantity and quality of developing memory T cells. Immunological rules guiding subunit vaccine elicited T cell responses would not be very different from those guiding infection induced T cell responses. Hence, understanding infection in its natural settings could help in designing better antigen-adjuvant systems and strategies, for generating multifunctional memory responses. newlineIn our study we wished to obtain insights on the effects of fragmenting doses of antigen and adjuvant on memory T cell generation in a typical natural viral infection setting. We thus designed two objectives each focusing on initial/acute phase and contraction/resolution phase of infection. As part of first objective, we intended to mimic infection by administering TLR ligands as adjuvants and OVA as model antigen; following the course of infection. We immunized groups of C57BL/6 mice with combinations of TLR agonists (R848 + Poly I: C to mimic viral infection) along with Ag OVA by creating conditions analogous to graded inflammation and Ag dose. By adopting the modified approach, we found enhanced memory CD4+ T cell response