Adjuvanted SARS-CoV-2 Spike Protein Elicits Neutralizing Antibodies and CD4 T Cell Responses after a Single Immunization in Mice

Abstract Background SARS-CoV-2 has caused a global pandemic, infecting millions of people. A safe, effective vaccine is urgently needed and remains a global health priority. Subunit vaccines are used successfully against other viruses when administered in the presence of an effective adjuvant. Methods We evaluated three different clinically tested adjuvant systems in combination with the SARS-CoV-2 pre-fusion stabilized (S-2P) spike protein using a one-dose regimen in mice. Findings Whilst spike protein alone was only weakly immunogenic, the addition of either Aluminum hydroxide, a squalene based oil-in-water emulsion system (SE) or a cationic liposome-based adjuvant significantly enhanced antibody responses against the spike receptor binding domain (RBD). Kinetics of antibody responses differed, with SE providing the most rapid response. Neutralizing antibodies developed after a single immunization in all adjuvanted groups with ID50 titers ranging from 86–4063. Spike-specific CD4 T helper responses were also elicited, comprising mainly of IFN-γ and IL-17 producing cells in the cationic liposome adjuvanted group, and more IL-5- and IL-10-secreting cells in the AH group. Interpretation These results demonstrate that adjuvanted spike protein subunit vaccine is a viable strategy for rapidly eliciting SARS-CoV-2 neutralizing antibodies and CD4 T cell responses of various qualities depending on the adjuvant used, which can be explored in further vaccine development against COVID-19. Funding This work was supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.