Immune system development varies according to age, location, and anemia in African children

Area of Science:

• Immunology
• Pediatrics
• Vaccinology

Background:

• Vaccines are crucial for infectious disease prevention, especially in low- and middle-income countries.
• However, vaccines often exhibit reduced efficacy in these populations, necessitating research into factors influencing immune development.
• Understanding immune ontogeny is key to designing effective vaccines for at-risk children.

Purpose of the Study:

• To identify factors shaping immune system development in children under 5 years old in Tanzania and Mozambique.
• To correlate immune profiles with vaccine responses and health status (e.g., anemia).
• To compare immune development trajectories between African and European children.

Main Methods:

• Detailed immunophenotyping of longitudinal blood samples from children in the RTS,S malaria vaccine phase 3 trial.
• Comparison with the Generation R population-based cohort study in Dutch children.
• In vitro experiments to assess the impact of iron bioavailability on B cell function.

Main Results:

• Immune system composition dynamically changes during early childhood, influenced by geographical location.
• Tanzanian children showed altered immune cell development rates compared to Dutch children.
• High antibody responses to RTS,S/AS01E vaccine correlated with an activated immune profile (plasmablasts, T follicular helper cells).
• Anemia was associated with reduced frequencies of thymic emigrant T cells, memory B cells, and plasmablasts, which could be replicated in vitro by modulating iron.

Conclusions:

• Immune system composition in children is significantly influenced by age, geographical location, and anemia status.
• Anemia impairs specific B cell populations crucial for vaccine responses.
• These findings highlight the need to consider host factors for optimizing vaccine design and efficacy in diverse pediatric populations.