Immunogenicity of the Xcl1-SARS-CoV-2 Spike Fusion DNA Vaccine for COVID-19

SARS-CoV-2 spike (S) variants that may evade antibody-mediated immunity are emerging. Evidence shows that vaccines with a stronger immune response are still effective against mutant strains. Here, we report a targeted type 1 conventional dendritic (cDC1) cell strategy for improved COVID-19 vaccine design. cDC1 cells specifically express X-C motif chemokine receptor 1 (Xcr1), the only receptor for chemokine Xcl1. We fused the S gene sequence with the Xcl1 gene to deliver the expressed S protein to cDC1 cells. Immunization with a plasmid encoding the S protein fused to Xcl1 showed stronger induction of antibody and antigen-specific T cell immune responses than immunization with the S plasmid alone in mice. The fusion gene-induced antibody also displayed more powerful SARS-CoV-2 wild-type virus and pseudovirus neutralizing activity. Xcl1 also increased long-lived antibody-secreting plasma cells in bone marrow. These preliminary results indicate that Xcl1 serves as a molecular adjuvant for the SARS-CoV-2 vaccine and that our Xcl1-S fusion DNA vaccine is a potential COVID-19 vaccine candidate for use in further translational studies.

Automated summary

This study presents a targeted strategy for improved COVID-19 vaccine design using type 1 conventional dendritic (cDC1) cells. By fusing the S protein with the Xcl1 gene, the expressed S protein can be delivered to cDC1 cells, resulting in stronger immune responses and neutralizing activity against SARS-CoV-2 in a mouse model. These findings suggest that Xcl1 serves as a potential molecular adjuvant for SARS-CoV-2 vaccines.