Abstract
BackgroundDENV is the most globally prevalent mosquito-transmitted virus. Induction of a broadly and potently immune response is desirable for dengue vaccine development. MethodsSeveral formulations of secreted tetravalent EDIII protein containing different amounts of antigen from eukaryotic cells were used to evaluate the immune responses in mice. ResultsWe 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 protein were functional in clearing DENV-2 in circulation of mice. ConclusionsWe believe that the tetravalent secreted EDIII protein is a potential vaccine candidate against DENV and suggest further detailed studies of this formulation in nonhuman primates.
Highlights
DENV is the most globally prevalent mosquito-transmitted virus
Our results indicated that effective immune responses were generated in rEDIII-immunized mice, highlighting its functionality as a promising tetravalent dengue vaccine candidate, which could be potentially applied in DENV hyperendemic areas
All mice immunized with the tetravalent rEDIII protein developed an anti-envelope domain III (EDIII) IgG response against all four DENV serotypes (Fig. 1A-D)
Summary
DENV is the most globally prevalent mosquito-transmitted virus. Induction of a broadly and potently immune response is desirable for dengue vaccine development. Dengue virus infection is an arthropod-borne viral disease caused by dengue viruses which are transmitted by the bites of infected mosquitoes Aedes aegypti and Aedes albopictus [1, 2]. Primary infection with any one DENV serotype confers life-long immunity to that serotype, whereas secondary infection with a different serotype can cause the severe forms of the disease because of antibody-dependent enhancement (ADE) [9,10,11]. It is necessary for an effective DENV vaccine to induce a balanced and durable immune response specific for all four DENV serotypes simultaneously, avoiding the risk of severe disease through ADE. Development of a tetravalent dengue vaccine inducing balanced and long-life immunity is still a huge challenge
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