Utilization of Staphylococcal Immune Evasion Protein Sbi as a Novel Vaccine Adjuvant
| العنوان: | Utilization of Staphylococcal Immune Evasion Protein Sbi as a Novel Vaccine Adjuvant |
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| المؤلفون: | Yang, Yi, Back, Catherine R., Sartbaeva, Asel, Watts, Andrew G., Marchbank, Kevin J., van den Elsen, Jean M. H., Gräwert, Melissa A., Wahid, Ayla A., Denton, Harriet, Kildani, Rebecca, Paulin, Joshua, Wörner, Kristin, Kaiser, Wolgang, Svergun, Dmitri I. |
| المصدر: | Frontiers in Immunology, Vol 9 (2019) Yang, Y, Back, C R, Gräwert, M A, Wahid, A A, Denton, H, Kildani, R, Paulin, J, Wörner, K, Kaiser, W, Svergun, D I, Sartbaeva, A, Watts, A G, Marchbank, K J & Van Den Elsen, J M H 2019, ' Utilization of staphylococcal immune evasion protein sbi as a novel vaccine adjuvant ', Frontiers in Immunology, vol. 10, no. JAN, 3139 . https://doi.org/10.3389/fimmu.2018.03139 Frontiers in Immunology Yang, Y, Back, C, Gräwert, M, Wahid, A, Denton, H, Kildani, R, Paulin, J, Wörner, K, Kaiser, W, Svergun, D, Sartbaeva, A, Watts, A, Marchbank, K J & Van Den Elsen, J 2019, ' Utilization of Staphylococcal Immune Evasion Protein Sbi as a Novel Vaccine Adjuvant ', Frontiers in Immunology, vol. 9, 3139, pp. 1-17 . https://doi.org/10.3389/fimmu.2018.03139 Frontiers in immunology 9, 3139 (2019). doi:10.3389/fimmu.2018.03139 |
| بيانات النشر: | Frontiers Media S.A., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Models, Molecular, lcsh:Immunologic diseases. Allergy, Protein Conformation, Recombinant Fusion Proteins, Staphylococcus, Immunology, Complement, chemical and pharmacologic phenomena, Mice, Structure-Activity Relationship, SDG 3 - Good Health and Well-being, Adjuvants, Immunologic, Bacterial Proteins, adjuvant, vaccine, Animals, Immunology and Allergy, complement, ddc:610, Adjuvant, Original Research, immune evasion, Mice, Knockout, Antigens, Bacterial, Immune evasion, Staphylococcal Vaccines, Staphylococcal Infections, Disease Models, Animal, Staphycoccus aureus, Immunization, Carrier Proteins, lcsh:RC581-607, Vaccine, Acyltransferases |
| الوصف: | Co-ligation of the B cell antigen receptor with complement receptor 2 on B-cells via a C3d-opsonised antigen complex significantly lowers the threshold required for B cell activation. Consequently, fusions of antigens with C3d polymers have shown great potential in vaccine design. However, these linear arrays of C3d multimers do not mimic the natural opsonisation of antigens with C3d. Here we investigate the potential of using the unique complement activating characteristics of Staphylococcal immune-evasion protein Sbi to develop a pro-vaccine approach that spontaneously coats antigenswith C3 degradation products in a natural way. We show that Sbi rapidly triggers the alternative complement pathway through recruitment of complement regulators, forming tripartite complexes that act as competitive antagonists of factor H, resulting in enhanced complement consumption. These functional results are corroborated by the structure of the complement activating Sbi-III-IV:C3d:FHR-1 complex. Finally, we demonstrate that Sbi, fused with Mycobacterium tuberculosis antigen Ag85b, causes efficient opsonisation with C3 fragments, thereby enhancing the immune responsesignificantly beyond that of Ag85b alone, providing proof of concept for our pro-vaccine approach. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::b1a08cb3712cc821e8dfd1797e1a2702 https://www.frontiersin.org/article/10.3389/fimmu.2018.03139/full |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....b1a08cb3712cc821e8dfd1797e1a2702 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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