A dose-response study in mice of a tetravalent recombinant dengue envelope domain III protein secreted from insect cells

Background: DENV is the most globally prevalent mosquito-transmitted virus. Induction of a broadly and potently immune response is desirable for dengue vaccine development. Methods: We constructed a secreted tetravalent EDⅢ protein from eukaryotic cells and established a MAC-ELISA method for DENV diagnosis. This work aimed to evaluate the immune responses in mice of several formulations of rEDIII containing different amounts of the tetravalent protein. Results: We demonstrated that the tetravalent protein induced humoral immunity against all four serotypes of DENV, even at the lowest dose assayed. Besides, cellular immunities against DENV-1 and DENV-2 were elicited by medium dose group. Importantly, the immune responses induced by the tetravalent formulation were functional in clearing DENV-2 in circulation of mice. Conclusions: We believe that the tetravalent formulation of secreted EDⅢ protein is a potential vaccine candidate against DENV and suggest further detailed studies of this formulation in nonhuman primates. Keywords: Dengue virus; Tetravalent; Humoral immunity; Cellular immunity; Vaccine