Harnessing Chlamydia trachomatis-Specific Immunity: Integrating Immunopeptidomics and Vaccination Strategies to Recruit and Enhance CD8+ T Cell Responses

Chlamydia trachomatis (C. trachomatis), the leading cause of sexually transmitted bacterial infections globally, poses significant challenges in vaccine development due to its complex life cycle and interactions with the host. The bacterium forms a protective replication niche called an inclusion within host cells, evading immune defenses. Occasionally, "leakages" expose the bacterium or its antigens to the cytoplasm, aiding antigen processing. CD8+ T cells play a critical role in immune protection by inducing long-lasting memory during infection and vaccination, as outlined in Chapter I. Chapter II harnesses advanced mass spectrometry technology to investigate the immunopeptidome of human cells infected with C. trachomatis, revealing key features of the presented peptide library during infection and highlighting the pathogen-host immune system interactions. Chapters III and IV explore the potential of nucleic acid vaccines to stimulate efficient cellular immune responses through a prime-boost strategy, demonstrating the effectiveness of these vaccines in generating robust humoral and cellular immunity against intracellular pathogens. In Chapters V and VI, bacterial component-based vaccines, particularly outer membrane vesicles and particulate inclusion bodies, are examined for their ability to induce potent immune responses in mouse models. The novel particulate bodies platform showed significant promise in protecting against infection in challenge experiments, emphasizing its potential as a versatile and effective vaccination strategy. Overall, this thesis integrates various innovative vaccine platforms and an optimized antigen identification method, advancing our understanding of immune responses against C. trachomatis and paving the way for more effective vaccine development. The immunopeptidomics analysis using the inSPIRE-Select pipeline broadened the range of pathogen peptides identified, which could be critical for future vaccine design. By combining multiple antigens, optimizing delivery platforms, and balancing cellular and humoral responses, these approaches hold promise for developing a comprehensive and effective vaccine against C. trachomatis. Further research is needed to evaluate the long-term protection and clinical efficacy of these vaccines in human trials.