Understanding the Natural Immune Responses Against Malaria in Children and Pregnant Women in Light of Recent Vaccine Trials

Abstract

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites that disproportionately affects the poor, children, and pregnant women. The disease burden of malaria remains especially high in Africa where 85% of malaria cases occur. Recently, a promising vaccine candidate, called RTS, S/AS01, became the first malaria vaccine to reach phase III clinical trials and has shown remarkable progress in reducing morbidity in infants in highly endemic areas of Sub-Saharan Africa. In smaller phase II clinical trials, the vaccine showed a 62% reduction in episodes of clinical malaria in 6-12 week old infants. In addition, previous results from the phase III clinical trial showed a 55.8% reduction in episodes of clinical malaria in 5-17 month old infants. However, the most recent results from the phase III clinical trial showed only a 31% reduction in episodes of clinical malaria in 6-12 week old infants. As the vaccine is expected to be licensed and released in 2015, it is an opportune time to reflect on the factors that contribute toward the observed variation in vaccine efficacy. This thesis reviews the lessons and challenges in controlling malaria and eliciting protective immunity in children and pregnant women. I argue that developing effective malaria vaccines will be more feasible with a deeper understanding of the natural acquisition of immunity in individuals living in endemic areas. This thesis pinpoints two factors, age and transmission intensity, that affect the natural immune responses to parasitemia in humans. I further explore the role of these factors in field and case studies in the scientific literature as well as in the recent vaccine trials. The findings of this thesis suggest that further investigation into these factors that influence natural immune responses will contribute toward our understanding of the differential immune responses observed in the large vaccine clinical trials and the development of an effective malaria vaccine for children and pregnant women.