Assessment of adjuvantation strategy of lipid squalene nanoparticles for enhancing the immunogenicity of a SARS-CoV-2 spike subunit protein against COVID-19

https://doi.org/10.1016/j.ijpharm.2021.121024Get rights and content

Highlights

  • The adjuvant efficacy of lipid squalene nanoparticles (SQ@NPs) was assessed in mice.

  • One dose of S-protein with SQ@NPs works as well as two doses of S-protein alone.

  • SQ@NPs rephrase the activation of T cells.

  • The SQ@NP-adjuvanted vaccine is considerably tolerated via i.m. injection in mice.

Abstract

Vaccination is regarded as the most effective intervention for controlling the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study is to provide comprehensive information on lipid squalene nanoparticle (SQ@NP)-adjuvanted COVID-19 vaccines regarding modulating immune response and enhancing vaccine efficacy. After being adjuvanted with SQ@NP, the SARS-CoV-2 spike (S) subunit protein was intramuscularly (i.m.) administered to mice. Serum samples investigated by ELISA and virus neutralizing assay showed that a single-dose SQ@NP-adjuvanted S-protein vaccine can induce antigen-specific IgG and protective antibodies comparable with those induced by two doses of nonadjuvanted protein vaccine. When the mice received a boosting vaccine injection, anamnestic response was observed in the groups of adjuvanted vaccine. Furthermore, the secretion of cytokines in splenocytes, such as interferon (IFN)-γ, interleukin (IL)-5 and IL-10, was significantly enhanced after adjuvantation of S-protein vaccine with SQ@NP; however, this was not the case for the vaccine adjuvanted with conventional aluminum mineral salts. Histological examination of injection sites showed that the SQ@NP-adjuvanted vaccine was considerably well tolerated following i.m. injection in mice. These results pave the way for the performance tuning of optimal vaccine formulations against COVID-19.

Graphical abstract

Lipid squalene nanoparticles (SQ@NPs) play a crucial role in the immunogenicity of the SARS-CoV-2 spike subunit protein against COVID-19. In a mouse model, we found that one dose of the S-protein with SQ@NPs works as well as two doses of the S-protein alone without compromising safety aspects following i.m. injection. These results pave the way for optimal vaccine formulations against COVID-19.

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Keywords

COVID-19 vaccine
Immunomodulation
Lipid squalene nanoparticles
Single injection
Vaccine adjuvant

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1

These authors contributed equally to this work.

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