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

Int J Pharm. 2021 Sep 25:607:121024. doi: 10.1016/j.ijpharm.2021.121024. Epub 2021 Aug 18.

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.

Keywords: COVID-19 vaccine; Immunomodulation; Lipid squalene nanoparticles; Single injection; Vaccine adjuvant.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19*
  • Humans
  • Lipids
  • Mice
  • Nanoparticles*
  • SARS-CoV-2
  • Squalene

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Lipids
  • Squalene