1. Nanoparticular CpG-adjuvanted SARS-CoV-2 S1 protein elicits broadly neutralizing and Th1-biased immunoreactivity in mice
- Author
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Tein-Yao Chang, Hui-Tsu Lin, Jenn-jong Young, Szu-Cheng Kuo, Xin-an Chen, Cheng-Cheung Chen, and Der-Jiang Chiao
- Subjects
Antigenicity ,COVID-19 Vaccines ,CpG Oligodeoxynucleotide ,Immunogenicity enhancement ,Antibodies, Viral ,Biochemistry ,Article ,Immunoglobulin G ,Mice ,Immunogenicity, Vaccine ,Adjuvants, Immunologic ,Antigen ,Structural Biology ,Fucoidan-trimethylchitosan nanoparticles ,Animals ,Neutralizing antibody ,Molecular Biology ,Mice, Inbred BALB C ,biology ,SARS-CoV-2 ,Chemistry ,SARS-CoV-2 infection ,Immunogenicity ,Th1-biased cellular immune responses ,General Medicine ,Th1 Cells ,respiratory system ,Virology ,Oligodeoxyribonucleotides ,CpG site ,Recombinant S1 protein ,Spike Glycoprotein, Coronavirus ,biology.protein ,Nanoparticles ,CpG adjuvant ,FluoroSpot ,Broadly Neutralizing Antibodies - 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.
- Published
- 2021