Enhanced Humoral and Cellular Immune Responses Elicited by <i>Salmonella</i> Flagellin-Adjuvanted SARS-CoV-2 S1 Subunit Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been spreading and changing globally. Adjuvant-based vaccines can improve vaccine protection by enhancing the immune response. Bacterial flagellin is a potent adjuvant and promotes protective immune responses. Here, we successfully expressed and purified the S1 subunit of SARS-CoV-2. The adjuvanticity of flagellin (FliC) of <i>Salmonella</i> Typhimurium in mice was determined by combining it with the recombinant S1 subunit vaccine. FliC-adjuvanted S1 vaccine could induce significantly enhanced S1-specific Immunoglobulin G (IgG), IgG1 and IgG2a titers, SARS-CoV-2-neutralizing antibodies, and levels of Th1 type (TNF-α and IFN-γ) and Th2 type (Interleukin-5 (IL-5), IL-4, IL-10, and IL-13) cytokines in splenocytes compared with the S1 alone group. Additionally, the titers of S1-specific IgG antibodies in the FliC adjuvant group could maintain a high level for at least 2 months. These results indicated that the FliC-adjuvanted S1 subunit vaccine could trigger strong humoral and cellular immune responses, which could promote the ongoing development of COVID-19 vaccines.