Effect of chemokine MIP3α fusion to SARS-CoV-2 spike protein receptor binding domain antigen on the response to a SARS-CoV-2 vaccine

This study introduced a DNA vaccine construct encoding fusion of macrophage inflammatory protein-3α (MIP3α) to SARS-CoV-2 spike protein receptor binding domain (RBD) in BALB/c mice. Previous studies in our laboratory have shown that either humoral or cellular immune responses were enhanced by vaccines with MIP3α, which interacts with the sixth CC chemokine receptor (CCR6), fused to the antigens for malaria and melanoma, respectively. Given that the COVID-19 pandemic has disrupted lives throughout the world and the fact that many SARS-CoV-2 variants capable of escaping from antibody neutralization activities have been emerging since the start of the pandemic, it is of urgent need to investigate vaccine platforms through which higher concentration and/or more sustained antibodies can be elicited. It is also important to generate T-cell responses to prevent the onset of severe disease and the need for hospitalizations. There are two parts in this study: a dose-response mouse experiment investigating the role vaccine doses play on immunity, and an intranasal mouse experiment examining the RBD-MIP3α as a nasal vaccine. Results suggest that fusion of MIP3α to RBD can either enhance the humoral or cellular response, when administered via the intramuscular (IM) or intranasal (IN) route, respectively. Specifically, antibody responses are greater and have a longer duration in mice receiving the RBD-MIP3α vaccine IM than in mice receiving the RBD-only vaccine IM, especially when the vaccines are given at a lower dose for each vaccination. Moreover, when serving as a nasal vaccine, RBD-MIP3α also enhances the T-cell response