Bioengineered chimeric VLPs targeting chikungunya virus and SARS-CoV-2 show high immunogenicity in mice.

The SARS-CoV-2 pandemic supercharged global efforts towards cutting-edge vaccination strategies for current threats and emerging viruses. It is imperative to develop and investigate next-generation vaccines such as chimeric Virus-Like Particles (chi-VLPs) vaccines for increased immunogenicity, ease of production, and scalability to supplement the worldwide vaccine supply. This study reports a novel bivalent vaccine design of Chimeric Alphavirus-Coronavirus Virus-Like Particles (ChAC-VLPs), displaying fusion glycoproteins of Chikungunya virus (CHIKV) and a Receptor Binding Domain (RBD) of SARS-CoV-2 on its surface. The uniqueness and versatility of ChAC-VLPs have been demonstrated via various techniques, including Western blot, Immunofluorescence, cryo-EM, and Dynamic Light Scattering (DLS). The multimeric epitope display of immunogenic antigens was validated by cell-based assays. ChAC-VLP immunized mice sera have shown substantial neutralization titers for CHIKV (PRNT50 of 1:25). Similarly, serum antibodies were detected for SARS-CoV-2 RBD as observed by antigen-specific ELISA and validated using Surface Plasmon Resonance (SPR). ChAC-VLP-immunized mice sera at a 1:10 dilution exhibited 80-95 % SARS-CoV-2 pseudovirus neutralization relative to the untreated virus control. In conclusion, this study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infections and contributes valuable insights into the chi-VLPs domain and its design.