Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity
| Autor: | Santa-Mariela Olivera-Ugarte, Marie-Eve Laliberté-Gagné, Pierre Savard, Denis Leclerc, Marilène Bolduc, Caroline Garneau |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology lcsh:Medicine Peptide vaccine platform Article Epitope sortase (SrtA) 03 medical and health sciences 0302 clinical medicine Immune system Antigen Drug Discovery Cytotoxic T cell Pharmacology (medical) Pharmacology chemistry.chemical_classification influenza nucleocapsid Innate immune system biology Chemistry allergology Immunogenicity lcsh:R rod-shaped nanoparticle biology.organism_classification papaya mosaic virus (PapMV) Cell biology 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis influenza M2e Papaya mosaic virus |
| Zdroj: | Vaccines Vaccines, Vol 9, Iss 33, p 33 (2021) Volume 9 Issue 1 |
| Popis: | Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles. |
| Databáze: | OpenAIRE |
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