Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice

Autor: Katharina Wørzner, Daniel J. Sheward, Signe Tandrup Schmidt, Leo Hanke, Julie Zimmermann, Gerald McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell, Dennis Christensen, Gabriel Kristian Pedersen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: EBioMedicine, Vol 63, Iss , Pp 103197- (2021)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2020.103197
Popis: 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.
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