Construction of multi-epitope based anti-dengue virus vaccine and its impact on cell mediated immune response in vitro

Abstract

The frequent epidemics and endemics caused by Dengue virus have imposed a threat on global health. The risk of antibody dependent enhancement (ADE) associated with four different serotypes of DENV is the footprint in serious illnesses like Dengue hemorrhagic fever and dengue shock syndrome. The death rate caused by DENV has also been escalated due to lack in treatment and inadequate prevention of the disease. There is an ultimate failure due to improper and trivial measures to control the vector (mosquito) spread. Such circumstances demand an effective vaccine to not only prevent the outbreaks, but also outrageous diseases caused by DENV. Vaccination and immunization have been always a choice to prevent infectious disease. However, developing a vaccine against DENV is difficult as it has to effective against all of its serotypes. A tetravalent vaccine is not only a need to combat all of the circulating serotypes infections but to eliminate the risk of ADE. To circumvent the laborious and expensive vaccine construction like live attenuated vaccines, mRNA has been selected to accomplish the objective. This research utilized multiple epitopes from DENV envelope, which is highly immunogenic, to construct mRNA vaccine against all serotypes of DENV. The mRNA was transcribed in vitro and transfected into peripheral blood mononuclear cells PBMCs to determine its immunogenicity. The in vitro transcribed mRNA proved to increase the mRNA levels of both T helper 1 (TH1) response inducer, interlukin-12 and TH1 cytokine interferon gamma which illustrates the generation of memory T lymphocytes. Thus, it is a promising candidate to be evaluated further as a vaccine against DENV.