Th17 Cells Are Not Required for Host Defense Against Murine Disseminated Candidiasis, But Are Required for Vaccine-Mediated Protection (132.10)

Abstract Background: We are developing a vaccine based on the recombinant N-terminus of the candidal adhesin, Als3p (rAls3p-N), which results in significant protection against disseminated candidiasis. Vaccine protection requires upstream T lymphocytes and downstream functional phagocytes. We therefore sought to determine the role of Th17 cells in vaccine-mediated protection. Methods: We compared Th1 (CD4+IFN- ƒ×+), Th17 (CD4+IL-17+), and Th1/17 (CD4+IFN- ƒ×+IL-17+) cell frequencies in mice vaccinated with rAls3p-N + Al(OH)3 or Al(OH)3 adjuvant alone. We also compared vaccine efficacy in IL-17 deficient, CCR6 (cell surface marker of Th17 cells) deficient, or congenic wild type control mice infected via the tail-vein with C. albicans. Results: Vaccination increased Th1, Th17, and Th1/Th17 frequencies in mice. Splenocytes from vaccinated mice stimulated with rAls3p-N ex vivo produced significantly higher levels of IFN- ƒ×, IL-17, and KC than splenocytes from control mice. IL-17 and CCR6 deficient mice were not more susceptible to disseminated candidiasis than control mice. However, vaccine efficacy was abrogated in both IL-17 and CCR6 deficient mice. Conclusion: Th17 cells are not required for host defense against disseminated candidiasis in unvaccinated mice. However, the rAls3p-N vaccine stimulates Th17 and Th1/17 cells, and Th17 cells are required for vaccine efficacy in mice.