Abstract
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.
Highlights
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
While live attenuated virus (LAV) vaccines have been the candidate of choice in the past, recent advances in molecular biology has demonstrated the effectiveness of other vaccine platforms especially Virus Like Particles (VLPs)
To the best of our knowledge, this is the first study demonstrating the effectiveness of Capsid protein containing VLPs for Yellow fever (YFV) and JEV as well as the first report demonstrating the efficacy of a multivalent VLP vaccine candidate against arboviruses
Summary
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. 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 JEV2. To the best of our knowledge, this is the first study demonstrating the effectiveness of Capsid protein containing VLPs for YFV and JEV as well as the first report demonstrating the efficacy of a multivalent VLP vaccine candidate against arboviruses. Our study demonstrates the feasibility of a multivalent VLP vaccine to provide neutralizing antibody response against diverse arboviruses
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