The immune divide: factors influencing immune variation and differences in vaccine responses

Pyuza, J.J. (2025)

Doctoral Thesis

Human immune responses to vaccination differ widely across populations due to a combination of genetic, environmental, and microbial influences. This thesis investigates the sources of immune variation and their relationship with yellow fever (YF) vaccine antibody responses in healthy Tanzanian adults from distinct rural and urban settings. Using the YF vaccine as a model, the study integrates baseline immune cell profiling, gut microbiota analysis, and lifestyle data to identify non-genetic determinants of vaccine responsiveness.
Immune cell distributions measured by mass and flow cytometry revealed significant differences between rural and urban participants, reflecting contrasting environmental exposures and living conditions. Higher baseline frequencies of classical monocytes were associated with stronger YF antibody responses. Gut microbiota composition clustered independently of residence and explained more variability in vaccine immunogenicity than geographic location alone. Antibody titers were initially high but waned over time.
These findings highlight that immune variation within African populations is strongly influenced by lifestyle, microbial, and ecological factors. Incorporating baseline immune and microbial profiling into vaccine studies may improve understanding of population-specific determinants of immunogenicity and guide more context-appropriate vaccination strategies.

• Immune variation
• Yellow fever vaccine
• Antibody response
• Baseline immune profiling
• Classical monocytes
• Gut microbiota
• Lifestyle factors
• Urban–rural differences
• Vaccine immunogenicity
• Tanzania.

• All authors: Pyuza, J.J.
• Supervisor: Yazdanbakhsh, M.; Hogendoorn, P.C.W.
• Co-supervisor: Jochems, S.P.
• Committee: Arens, R.; Miranda, N.F. de; Roestenberg, M.; Adegnika, A.A.; Masenga, G.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2025-11-25
• ISBN (print): 9789465109053
• DOI: doi:10.60602/1QZM-MJ30
• Sponsorship: LUMC Global given to Jeremia Pyuza; The Spinoza Prize and the European Research Council (ERC) Advanced Grant from the European Commission to Prof. Maria Yazdanbakhsh