COBRA-Based Dengue Tetravalent Vaccine Elicits Neutralizing Antibodies Against All Four Dengue Serotypes

Dengue virus (DENV) is the most common arthropod-borne infection in the world. The co-circulation of four serotypes, complex pathogenesis, and potential for antibody-enhanced disease has made vaccine development efforts difficult. To ensure protection and minimize vaccine-related disease augmentation, a DENV vaccine must provide equivalent immunity to all four serotypes. Four different vaccine formulations were evaluated for efficacy and utility. DNA plasmid based and purified subviral particles (SVP) vaccines were designed using prototype sequences as well as consensus algorithms known as computationally-optimized broadly reactive antigen (COBRA). These vaccines were formulated against each individual serotype, as well as tetravalent mixtures and used to inoculate mice. All monovalent vaccines elicited neutralizing antibodies against each of their specific homologous virus. In contrast, only purified versions of tetravalent subviral particle (SVP) elicited high levels of neutralizing antibodies against all four serotypes. All Dengue COBRA VLP vaccines elicit a broadly reactive immune response against all four subtypes of dengue virus. A non-infectious SVP vaccine that induces immune protection against the four DENV serotypes could provide a safer alternative candidate to live attenuated viruses.