Mosquito borne viral diseases are an emerging threat as evident from the recent outbreak of Zika virus (ZiKV) as well as repeated outbreaks of chikungunya (cHiKV), Yellow fever (YfV) and Japanese encephalitis (JEV) virus in different geographical regions. These four arboviruses are endemic in overlapping regions due to the co-prevalence of the transmitting mosquito vector species Aedes and Culex. Thus, a multivalent vaccine that targets all four viruses would be of benefit to regions of the world where these diseases are endemic. We developed a potential Virus Like Particle (VLP) based multivalent vaccine candidate to target these diseases by using stable cell lines that continuously secrete VLps in the culture supernatants. Moreover, inclusion of Capsid in the VLPs provides an additional viral protein leading to an enhanced immune response as evident from our previous studies with ZIKV. Immunization of Balb/c mice with different combinations of Capsid protein containing VLPs either as monovalent, bivalent or tetravalent formulation resulted in generation of high levels of neutralizing antibodies. Interestingly, the potential tetravalent VLP vaccine candidate provided strong neutralizing antibody titers against all four viruses. The 293 T stable cell lines secreting VLPs were adapted to grow in suspension cultures to facilitate vaccine scale up. Our stable cell lines secreting individual VLPs provide a flexible yet scalable platform conveniently adaptable to different geographical regions as per the need. Further studies in appropriate animal models will be needed to define the efficacy of the multivalent vaccine candidate to protect against lethal virus challenge.Arthropod borne viruses are a group of pathogens that are transmitted in the human population via the bite of arthropods including mosquitoes, flies and ticks. Recent increase in arboviral epidemics in the human population has been attributed to various factors including urbanization and geographical expansion of both the host and vectors for these diseases 1,2 . Amongst these arboviral diseases, Chikungunya (CHIKV), Japanese Encephalitis (JEV), Yellow Fever (YFV) and Zika virus (ZIKV) have expanded from isolated outbreaks in endemic areas to large scale epidemics affecting multiple continents 3,4 . The recent outbreaks of ZIKV 5 and previous outbreaks of CHIKV 6 are indications that these viruses will continue to plague the human population putting millions at risk and adding a significant burden on the healthcare system.The World Health Organization lists Dengue virus (DENV) as the most common mosquito-borne viral disease with CHIKV, YFV and JEV as other arboviruses being endemic in various parts of the world. The majority of human population that resides in the tropical and subtropical regions of the world is at risk for at least one of these arboviral infections. These pathogens are transmitted via vectors that are found in overlapping geographical regions; Aedes sp in the case of CHIKV, YFV and ZIKV and Culex sp in the case of JEV 2 . Furthermore, ...
The recent outbreaks of Zika virus (ZIKV) infections and associated microcephaly in newborns has resulted in an unprecedented effort by researchers to target this virus. Significant advances have been made in developing vaccine candidates, treatment strategies and diagnostic assays in a relatively short period of time. Being a preventable disease, the first line of defense against ZIKV would be to vaccinate the highly susceptible target population, especially pregnant women. Along those lines, several vaccine candidates including purified inactivated virus (PIV), live attenuated virus (LAV), virus like particles (VLP), DNA, modified RNA, viral vectors and subunit vaccines have been in the pipeline with several advancing to clinical trials. As the primary objective of Zika vaccination is the prevention of vertical transmission of the virus to the unborn fetus, the safety and efficacy requirements for this vaccine remain unique when compared to other diseases. This review will discuss these recent advances in the field of Zika vaccine development.
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