An intact signal peptide on dengue virus E protein enhances immunogenicity for CD8(+) T cells and antibody when expressed from modified vaccinia Ankara.

Abstract

Dengue is a global public health concern and this is aggravated by a lack of vaccines or antiviral therapies.Despite the well-known role of CD8+T cells in the immunopathogenesis of Dengue virus (DENV), onlyrecent studies have highlighted the importance of this arm of the immune response in protection againstthe disease. Thus, the majority of DENV vaccine candidates are designed to achieve protective titers ofneutralizing antibodies, with less regard for cellular responses. Here, we used a mouse model to investi-gate CD8+T cell and humoral responses to a set of potential DENV vaccines based on recombinant modifiedvaccinia virus Ankara (rMVA). To enable this study, we identified two CD8+T cell epitopes in the DENV-3E protein in C57BL/6 mice. Using these we found that all the rMVA vaccines elicited DENV-specific CD8+T cells that were cytotoxic in vivo and polyfunctional in vitro. Moreover, vaccines expressing the E proteinwith an intact signal peptide sequence elicited more DENV-specific CD8+T cells than those expressingE proteins in the cytoplasm. Significantly, it was these same ER-targeted E protein vaccines that elicitedantibody responses. Our results support the further development of rMVA vaccines expressing DENV Eproteins and add to the tools available for dengue vaccine development