Molecular Hallmarks of Naturally Acquired Immunity to Malaria
Prospective studies of immune responses before, during, and after a given perturbation, whether by infection or vaccination, provide the clearest view of the relationship between immune response dynamics and clinical outcomes. In this regard, the analysis of vaccine studies is relatively easy to perform since blood samples can be collected from volunteers at pre-determined time points before and after vaccination. However, prospective studies of immune responses to most human pathogens are more difficult to conduct given the sporadic and/or infrequent nature of natural infections in human populations. In the case of malaria, Plasmodium falciparum (Pf) transmission in many malaria-endemic areas is sporadic or year-round; either scenario presents a challenge for investigating immune responses at defined time points relative to Pf infection in population-based studies. However, in the area of Mali where this study will be conducted, intense Pf transmission occurs during a predictable, discrete, 6-month malaria season from July through December. At the peak of the malaria season in October, the entomological inoculation rate in the area of Mali where this study will be conducted reaches 50 to 60 infective bites per person per month and then falls to near zero during the 6-month dry season. From previous studies in this area, ~90% of individuals are not infected with Pf just before the malaria season, but then >90% become infected with Pf at least once during the subsequent 6-month malaria season. Thus, a given immune parameter can be measured before, during, and after Pf infection, and it can be correlated with malaria immunity or susceptibility. The goal of this study is to investigate the mechanisms underlying naturally acquired malaria immunity by applying genomics-based tools to a cohort study in an area of intense, seasonal Pf transmission in Mali.
National Institute of Allergy and Infectious Diseases (NIAID)