Abstract
BackgroundCurrently, a licensed vaccine for Dengue Virus (DENV) is not yet available. Virus-like particles (VLP) have shown considerable promise for use as vaccines and have many advantages compared to many other types of viral vaccines. VLPs have been found to have high immunogenic potencies, providing protection against various pathogens.ResultsIn the current study, four DENV-VLP serotypes were successfully expressed in Pichia pastoris, based on co-expression of the prM and E proteins. The effects of a tetravalent VLP vaccine were also examined. Immunization with purified, recombinant, tetravalent DENV1-4 VLPs induced specific antibodies against all DENV1-4 antigens in mice. The antibody titers were higher after immunization with the tetravalent VLP vaccine compared to titers after immunization with any of the dengue serotype VLPs alone. Indirect immunofluorescence assay (IFA) results indicated that sera from VLP immunized mice recognized the native viral antigens. TNF-α and IL-10 were significantly higher in mice immunized with tetravalent DENV-VLP compared to those mice received PBS. The tetravalent VLP appeared to stimulate neutralizing antibodies against each viral serotype, as shown by PRNT50 analysis (1:32 against DENV1 and 2, and 1:16 against DENV3 and 4). The highest titers with the tetravalent VLP vaccine were still a little lower than the monovalent VLP against the corresponding serotype. The protection rates of tetravalent DENV-VLP immune sera against challenges with DENV1 to 4 serotypes in suckling mice were 77, 92, 100, and 100%, respectively, indicating greater protective efficacy compared with monovalent immune sera.ConclusionsOur results provide an important basis for the development of the dengue VLP as a promising non-infectious candidate vaccine for dengue infection.
Highlights
A licensed vaccine for Dengue Virus (DENV) is not yet available
The results indicate that tetravalent DENV-Virus-like particles (VLP) could be a promising vaccine candidate
Expression and purification of DENV-VLP Yeast lysates were analyzed for expression of E proteins by Western blot using mAbs as described in Methods
Summary
A licensed vaccine for Dengue Virus (DENV) is not yet available. 50 to 100 million new cases of dengue infection and 500,000 cases of DHF and/or DSS occur annually [3]. Prevention and control of widespread dengue infection has been a priority of the World Health Organization (WHO) for three decades; a licensed vaccine for DENV is not yet available [4]. Dengue fever can be caused by any one of these four serotypes and life-long immunity against a distinct serotype can be established after infection. The severe forms of DENV infection, DHF and DSS, often occur when individuals are infected a second time by a different serotype [5,6,7].
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