Abstract
We developed a novel platform to express high levels of recombinant lipoproteins with intrinsic adjuvant properties. Based on this technology, our group developed recombinant lipidated dengue envelope protein domain IIIs as vaccine candidates against dengue virus. This work aims to evaluate the immune responses in mice to the tetravalent formulation. We demonstrate that 4 serotypes of recombinant lipidated dengue envelope protein domain III induced both humoral and cellular immunity against all 4 serotypes of dengue virus on the mixture that formed the tetravalent formulation. Importantly, the immune responses induced by the tetravalent formulation in the absence of the exogenous adjuvant were functional in clearing the 4 serotypes of dengue virus in vivo. We affirm that the tetravalent formulation of recombinant lipidated dengue envelope protein domain III is a potential vaccine candidate against dengue virus and suggest further detailed studies of this formulation in nonhuman primates.
Highlights
Human vaccines, is incompetent to elicit complete protection against dengue virus infection[26,29,32]
TLED III induced high avidity index of antibody against all 4 serotypes of envelope protein domain III, which were comparable with each other. These results indicate the presence of a substantial concentration of high affinity antibodies against all 4 serotypes of envelope protein domain III in mice immunized with tLED III
We demonstrated that the performance of lipidated dengue envelope protein domain III is superior to its non-lipidated counterpart[38,39,40,41]
Summary
Human vaccines, is incompetent to elicit complete protection against dengue virus infection[26,29,32]. It has been shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages through toll-like receptors. We demonstrated that Escherichia coli-expressed lipoprotein stimulated innate immunity through the toll-like receptor 236 and induced superior adaptive immunity to its non-lipidated counterpart[35,37]. This lipidation approach has been applied to each serotype of ED III38–41, but a tetravalent formulation has not yet been characterized. Our results indicate that functional immune responses were generated in tLED III-immunized mice and suggest that tLED III is a potential tetravalent dengue vaccine candidate
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