Nanoparticular CpG-adjuvanted SARS-CoV-2 S1 protein elicits broadly neutralizing and Th1-biased immunoreactivity in mice

Int J Biol Macromol. 2021 Dec 15;193(Pt B):1885-1897. doi: 10.1016/j.ijbiomac.2021.11.020. Epub 2021 Nov 11.

Abstract

The spike (S) protein is a leading vaccine candidate against SARS-CoV-2 infection. The S1 domain of S protein, which contains a critical receptor-binding domain (RBD) antigen, potentially induces protective immunoreactivities against SARS-CoV-2. In this study, we presented preclinical evaluations of a novel insect cell-derived SARS-CoV-2 recombinant S1 (rS1) protein as a potent COVID-19 vaccine candidate. The native antigenicity of rS1 was characterized by enzyme-linked immunosorbent assay with a neutralizing monoclonal antibody targeting the RBD antigen. To improve its immunogenicity, rS1-adjuvanted with fucoidan/trimethylchitosan nanoparticles (FUC-TMC NPs) and cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODNs) were investigated using a mouse model. The S1-specific immunoglobulin G (IgG) titers, FluoroSpot assay, pseudovirus- and prototype SARS-CoV-2-based neutralization assays were assessed. The results showed that the rS1/CpG/ FUC-TMC NPs (rS1/CpG/NPs) formulation induced a broad-spectrum IgG response with potent, long-lasting, and cross-protective neutralizing activity against the emerging SARS-CoV-2 variant of concern, along with a Th1-biased cellular response. Thus, the rS1/CpG/NPs formulation presents a promising vaccination approach against COVID-19.

Keywords: CpG adjuvant; Fucoidan-trimethylchitosan nanoparticles; Immunogenicity enhancement; Neutralizing antibody; Recombinant S1 protein; SARS-CoV-2 infection; Th1-biased cellular immune responses.

MeSH terms

  • Adjuvants, Immunologic* / chemistry
  • Adjuvants, Immunologic* / pharmacology
  • Animals
  • Antibodies, Viral / immunology*
  • Broadly Neutralizing Antibodies / immunology*
  • COVID-19 Vaccines* / chemistry
  • COVID-19 Vaccines* / pharmacology
  • Immunogenicity, Vaccine*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Oligodeoxyribonucleotides* / chemistry
  • Oligodeoxyribonucleotides* / pharmacology
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus* / chemistry
  • Spike Glycoprotein, Coronavirus* / pharmacology
  • Th1 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • COVID-19 Vaccines
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Spike Glycoprotein, Coronavirus