Matias, Ciancaglini. Mechanisms of vectored vaccination for durable effector T cell immunity and sustained germinal center reactions. 2024, Doctoral Thesis, University of Basel, Faculty of Science.
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Official URL: https://edoc.unibas.ch/96832/
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Abstract
A deep understanding of the immunological mechanisms induced by vaccination, that lead to protective immunity, is essential for developing new vaccine platforms against current and emerging pathogens. The present thesis was aimed at gaining a better mechanistic understanding of how vaccines work. In the first part, we focused our study on the molecular determinants of viral vectors that account for long-lived CD8 T cell responses. In the second part, we performed a comparative analysis of COVID-19 vaccine regimens in clinical use, focusing on the induction and maintenance of GC responses. Finally, in the third part, we identified viral vectors that represent safer vaccine platforms, and tested their immunogenic capacity. this thesis offers a fundamental understanding of the mechanistic requirements of replication-deficient viral vectors for the induction of long-lived and potent CD8 T cell immunity.
We showed that non-cytolytic vectors can drive these responses through triggering of IFN-I, and should be chosen for the induction of durable CD8 T cell immunity. Furthermore, combining COVID-19 mRNA vaccinations in homologous prime-boost regimens favors the continued engagement of B cell clones in germinal centers and enhances the breadth of neutralizing antibodies compared to ChAdOx-1/mRNA or ChAdOx-1/ChAdOx-1 regimens. mRNA/mRNA regimens should be chosen in order to elicit variant cross-reactive antibody responses. Finally, the identification of PF4 non-binding adenoviral vectors offers new vaccine platforms with an improved safety profile.
We showed that non-cytolytic vectors can drive these responses through triggering of IFN-I, and should be chosen for the induction of durable CD8 T cell immunity. Furthermore, combining COVID-19 mRNA vaccinations in homologous prime-boost regimens favors the continued engagement of B cell clones in germinal centers and enhances the breadth of neutralizing antibodies compared to ChAdOx-1/mRNA or ChAdOx-1/ChAdOx-1 regimens. mRNA/mRNA regimens should be chosen in order to elicit variant cross-reactive antibody responses. Finally, the identification of PF4 non-binding adenoviral vectors offers new vaccine platforms with an improved safety profile.
Advisors: | Pinschewer, Daniel |
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Committee Members: | Bumann, Dirk and Kalinke, Ulrich |
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer) 05 Faculty of Science |
UniBasel Contributors: | Pinschewer, Daniel and Bumann, Dirk |
Item Type: | Thesis |
Thesis Subtype: | Doctoral Thesis |
Thesis no: | 15594 |
Thesis status: | Complete |
Number of Pages: | 143 |
Language: | English |
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edoc DOI: | |
Last Modified: | 23 Jan 2025 05:30 |
Deposited On: | 22 Jan 2025 14:16 |
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