Heterologous DNA Prime- Subunit Protein Boost with Chikungunya Virus E2 Induces Neutralizing Antibodies and Cellular-Mediated Immunity

Chikungunya virus (CHIKV) has become a significant public health concern due to the increasing number of outbreaks worldwide and the associated comorbidities. Despite substantial efforts, there is no specific treatment or licensed vaccine against CHIKV to date. The E2 glycoprotein of CHIKV is a promising vaccine candidate as it is a major target of neutralizing antibodies during infection. In this study, we evaluated the immunogenicity of two DNA vaccines (a non-targeted and a dendritic cell-targeted vaccine) encoding a consensus sequence of E2(CHIKV) and a recombinant protein (E2*(CHIKV)). Mice were immunized with different homologous and heterologous DNAprime-E2* protein boost strategies, and the specific humoral and cellular immune responses were accessed. We found that mice immunized with heterologous non-targeted DNA prime- E2*(CHIKV) protein boost developed high levels of neutralizing antibodies, as well as specific IFN-& gamma; producing cells and polyfunctional CD4(+) and CD8(+) T cells. We also identified 14 potential epitopes along the E2(CHIKV) protein. Furthermore, immunization with recombinant E2*(CHIKV) combined with the adjuvant AS03 presented the highest humoral response with neutralizing capacity. Finally, we show that the heterologous prime-boost strategy with the non-targeted pVAX-E2 DNA vaccine as the prime followed by E2* protein + AS03 boost is a promising combination to elicit a broad humoral and cellular immune response. Together, our data highlights the importance of E2(CHIKV) for the development of a CHIKV vaccine.

Automated summary

This study evaluated the immunogenicity of two DNA vaccines (a non-targeted and a dendritic cell-targeted vaccine) against CHIKV and highlights the importance of the E2(CHIKV) protein for the development of a CHIKV vaccine. The heterologous non-targeted DNA prime-E2*(CHIKV) protein boost strategy resulted in high levels of neutralizing antibodies, specific IFN-γ producing cells, and polyfunctional CD4(+) and CD8(+) T cells. Immunization with recombinant E2*(CHIKV) combined with the adjuvant AS03 presented the highest humoral response with neutralizing capacity. The non-targeted pVAX-E2 DNA vaccine prime followed by E2* protein + AS03 boost was identified as a promising combination to elicit a broad humoral and cellular immune response.