4.7 Article

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

Journal

EBIOMEDICINE
Volume 63, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ebiom.2020.103197

Keywords

SARS-CoV-2; Alum; Subunit vaccine; CAF (R) 01; MF59 (TM); Squalene emulsion; Neutralizing antibodies

Funding

  1. European Union Horizon 2020 research and innovation program [101003653]

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The study evaluated three different adjuvant systems combined with the SARS-CoV2 spike protein and found that they significantly enhanced antibody responses and neutralizing antibody titers. The oil-in-water emulsion system provided the most rapid response, with all adjuvanted groups developing neutralizing antibodies after a single dose. The specific CD4 T cell responses also varied depending on the adjuvant used.
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-CoV2 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-g 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. (C) 2020 The Author(s). Published by Elsevier B.V.

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