Co-delivery of lymphopoietic cytokines in live Salmonella vaccines enhances the T cell response (47.17)

Abstract

Abstract Live bacteria vaccine S. Typhi elicits strong mucosal and systemic immune responses. It is useful as a live vector to deliver heterologous antigens. Additionally, delivery of a eukaryotic expression vector by attenuated Salmonella leads to temporary expression of the coded gene in host cells after invasion. Because Salmonella invades preferentially macrophages and dendritic cells, the live bacteria could also be used to deliver immunomodulatory molecules to antigen-presenting cells. We hypothesize that co-delivery of lymphopoietic cytokine such as IL-2, IL-7 and IL-15, which has potential in promoting immune memory, enhances the efficacy of vaccination. Murine IL-2, IL-7 and IL-15 were cloned into eukaryotic expression vector pCMS-EGFP, and introduced into S. Typhi(F1), which carries Y. pestis protective antigen F1. Mice were immunized intranasally with above derivative strains, and boosted with purified antigen F1 in alum adjuvant Alhydrogel. This prime-boost strategy elicited strong mucosal and systemic antibody responses, as well as cell-mediated responses, e.g. antigen-specific proliferation and IFN-γ production of splenocytes. Inclusion of cytokine, however, further enhanced the cell-mediated responses. Antibody responses were not affected. Our data strongly support our hypothesis that production of lymphopoietic cytokine during priming vaccination promotes memory T cell responses.