Cellular immune profiles of Africans and Europeans in the context of vaccination and infectious diseases

Vaccines are a crucial preventive measure against infectious diseases, but their efficacy varies across populations due to genetic and environmental factors. The immunological markers explaining these differences in vaccine efficacy remain largely unexplored. This thesis investigates immune responses to novel vaccine candidates, using mass cytometry to identify key immune markers that can enhance vaccine strategies. In Chapter 2, the hookworm vaccine candidate Na-GST-1 was shown to induce TNF-producing effector-memory CD4 T cells expressing CD40L and CTLA-4. Blockade of CTLA-4 increased cytokine production, suggesting an inherent inhibitory effect. Chapter 3 assessed malaria immunity in German volunteers vaccinated with PfSPZ-CVac and Gabonese individuals with natural immunity. Elevated levels of CD56+ CD8 T cells and CD161+ CD4 T cells were linked to protection in both groups, with CD161+ CD4 T cells potentially associated with immunity after repeated malaria exposure. Chapters 4 and 5 examined cord blood responses in Gabonese populations, focusing on the impact of maternal infections. These studies revealed how environmental factors influence early immune development, particularly differences in innate immune cells and hematopoietic stem cells depending on maternal infection status. The findings underscore the significant role of environmental exposures in shaping immune responses and affecting vaccine efficacy.<br>