Virus-Like Particle-Based Multiserotype Quartet Vaccine of Dengue Envelope Protein Domain III Elicited Potent Anti-Dengue Responses

In this study, we presented two strategies for designing an envelope domain III (EDIII)-based tetravalent dengue virus (DENV) vaccine. The first approach was conjugation of the EDIIIs from all four DENV serotypes to a norovirus-like particle (NoV-LP) scaffold, yielding the NoV::tetEDIII vaccine. The second approach linked the EDIIIs of all four serotypes into a single polypeptide chain, which was also conjugated to the NoV-LP scaffold by using the SpyTag/SpyCatcher system, creating the NoV::quartetEDIII vaccine. These tetravalent DENV vaccines were evaluated for their immunogenicity against all DENV serotypes. Both vaccines elicited strong antibody responses against all serotypes in a prime-and-boost immunization regimen. Furthermore, the single-round infectious particle (SRIP) assay demonstrated that these antibodies had neutralizing capabilities superior to those of traditional subunit vaccines. Our study proposes a promising DENV vaccine strategy that may protect against all four serotypes, potentially promoting public health efforts to prevent and control dengue disease.