Reference - Detail
RRC ID | 81449 |
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Author | Chiu CT, Tsai HH, Chen JY, Hu CJ, Chen HW. |
Title | An Immunoreceptor-Targeting Strategy with Minimalistic C3b Peptide Fusion Enhances SARS-CoV-2 RBD mRNA Vaccine Immunogenicity. |
Journal | Int J Nanomedicine |
Abstract |
INTRODUCTION:The clinical success of mRNA vaccine during the COVID-19 pandemic has inspired emerging approaches to elevate mRNA vaccine immunogenicity. Among them, antigen fusion protein designs for improved immune cell targeting have been shown to augment humoral immunity against small antigen targets. METHODS:This research demonstrates that SARS-CoV-2 receptor binding domain (RBD) fusion with a minimalistic peptide segment of complement component 3b (C3b, residues 727-767) ligand can improve mRNA vaccine immunogenicity through antigen targeting to complement receptor 1 (CR1). We affirm vaccines' antigenicity and targeting ability towards specific receptors through Western blot and immunofluorescence assay. Furthermore, mice immunization studies help the investigation of the antibody responses. RESULTS:Using SARS-CoV-2 Omicron RBD antigen, we compare mRNA vaccine formulations expressing RBD fusion protein with mouse C3b peptide (RBD-mC3), RBD fusion protein with mouse Fc (RBD-Fc), and wild-type RBD. Our results confirm the proper antigenicity and normal functionality of RBD-mC3. Upon validating comparable antigen expression by the different vaccine formulations, receptor-targeting capability of the fusion antigens is further confirmed. In mouse immunization studies, we show that while both RBD-mC3 and RBD-Fc elevate vaccine immunogenicity, RBD-mC3 leads to more sustained RBD-specific titers over the RBD-Fc design, presumably due to reduced antigenic diversion by the minimalistic targeting ligand. CONCLUSION:The study demonstrates a novel C3b-based antigen design strategy for immune cell targeting and mRNA vaccine enhancement. |
Volume | 19 |
Pages | 7201-7214 |
Published | 2024-1-1 |
DOI | 10.2147/IJN.S463546 |
PII | 463546 |
PMID | 39050877 |
PMC | PMC11268571 |
MeSH | Animals Antibodies, Viral / blood Antibodies, Viral / immunology COVID-19 / immunology COVID-19 / prevention & control COVID-19 Vaccines* / administration & dosage COVID-19 Vaccines* / chemistry COVID-19 Vaccines* / immunology COVID-19 Vaccines* / pharmacology Female Humans Immunogenicity, Vaccine Mice Mice, Inbred BALB C Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / immunology Recombinant Fusion Proteins / pharmacology SARS-CoV-2* / immunology Spike Glycoprotein, Coronavirus / chemistry Spike Glycoprotein, Coronavirus / genetics Spike Glycoprotein, Coronavirus / immunology mRNA Vaccines |
Resource | |
Human and Animal Cells | 293T(RCB2202) |