Dokument: Characterization and immunogenicity of novel MVA-based vaccines against Chlamydia trachomatis in different mouse models
| Titel: | Characterization and immunogenicity of novel MVA-based vaccines against Chlamydia trachomatis in different mouse models | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=69987 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250701-112852-4 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Andreacchio, Giuseppe [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Drexler, Ingo [Gutachter] Prof. Dr. Kalscheuer, Rainer [Gutachter] | |||||||
| Stichwörter: | Modified Vaccinia virus Ankara, Vaccine, Chlamydia trachomatis, Immune response, T-cell response, Antibody response, Mouse models | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Chlamydia trachomatis is a leading cause of sexually transmitted infections worldwide and a major public health concern due to its prevalence and potential complications, including infertility and pelvic inflammatory disease, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. The MVA vector was engineered to express the C. trachomatis MOMP-based CTH522 antigen, a known target for immune responses against C. trachomatis. The vaccines were designed with two variations of the antigen: one in a secreted form (MVA-spCTH522) and the other in a membrane-anchored form (MVA-CTH522:B7). These variations were used to investigate how the localization of the antigen affects the immune response. The vaccine candidates were tested in two different mouse models: C57BL/6J mice, a standard strain widely used in immunological research, and HLA transgenic mice, which express human leukocyte antigen (HLA) molecules to better mimic human immune responses. This dual model evidenced how immune responses differ in a standard inbred mouse system compared to one that more closely associates with human immunology. In the C57BL/6J mouse model, both vaccines successfully induced CD4+ T cell responses, a critical component of the adaptive immune system. However, they did not induce significant antigen-specific CD8+ T-cell responses, which are often associated with the clearance of intracellular pathogens such as C. trachomatis. Notably, the membrane-anchored form of the vaccine, MVA-CTH522:B7, induced a more robust antibody response, particularly in the form of IgG2b and IgG2c antibodies, which are indicative of a Th1-directed immune response. This finding suggests that localization of the antigen to the cell membrane may enhance its immunogenicity. In the HLA transgenic mouse model, both vaccines demonstrated the ability to stimulate Th1- directed CD4+ T cells and multifunctional CD8+ T cells. However, only the MVA- CTH522:B7 vaccine induced a detectable antibody response in this model. This observation further confirms the importance of antigen localization in determining the nature and strength of the humoral immune response. The results of the study emphasize the critical role of antigen design for vaccine efficacy. The form and localization of the antigen significantly influenced the immune response, with the membrane-anchored form showing greater potential to induce both humoral and cellular immunity. The research also highlights the importance of selecting appropriate animal models for preclinical testing, as immune responses can vary widely between different systems. These results provide valuable insights into the development of vaccines against C. trachomatis. While the study provides a strong foundation for further research, it also highlights the complexity of vaccine development and the importance of using animal models which allow for immune responses that closely mimic the human immune response to better predict vaccine performance in humans. Future studies should investigate the efficacy of these vaccines in preventing C. trachomatis infection, assess their protective potential in challenge models, and evaluate different immunization strategies, including mucosal and systemic routes of administration. The research represents a significant step forward in addressing a pressing global health challenge and lays the groundwork for the development of effective vaccines against C. trachomatis. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 01.07.2025 | |||||||
| Dateien geändert am: | 01.07.2025 | |||||||
| Promotionsantrag am: | 01.04.2025 | |||||||
| Datum der Promotion: | 18.06.2025 |
