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 E2CHIKV 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-γ producing cells and polyfunctional CD4+ and CD8+ T cells. We also identified 14 potential epitopes along the E2CHIKV 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 E2CHIKV for the development of a CHIKV vaccine.

Meningoencephalitis Associated with Zika Virus and Chikungunya Virus Infection.

The etiology of viral meningoencephalitis is frequently unidentified. Chikungunya virus (CHIKV) and Zika virus (ZIKV) are known to affect the central nervous system and should therefore be considered in the diagnosis of meningoencephalitis, as its outcome may be influenced by the etiologic agent, age, and immunological condition of the patient. In this study, we aimed to determine whether CHIKV and ZIKV were the etiological agents of viral encephalitis in patients with meningoencephalitis admitted to the main hospital of infectious diseases in the city of Salvador, Brazil. Of the 1,049 patients with neurological symptoms who were admitted to the hospital during the study period, 149 were enrolled and 20 (13.34%) tested positive for ZIKV (12%) or CHIKV (1.34%). No specific clinical manifestations were observed to be associated with ZIKV or CHIKV infections. Determination of the etiological agent of meningitis and encephalitis is important for patient management and appropriate treatment.