The long-term objective of this field project based in two malaria endemic areas of western Kenya is to advance knowledge of how boosting effected by natural malaria infection influences T and B cell immune responses (cytokine ELISA and ELISPOT, B cell Ig production) to pre- erythrocytic and exo-erythrocytic Plasmodium falciparum antigens and resistance to re-infection in children and adults. T and B cell responses by residents of Siaya, where transmission is intense and perennial, will be compared with those of residents of the highlands in Uasin Gishu, where transmission is episodic and malaria epidemics occur. Using a combination of epidemiologic and immunologic tools, the specific aims of the project are to: 1. Determine whether the age-related frequencies of T and B cells specified by antigenic peptides of CSP, LSA1, and SSP2/TRAP differ according to cumulative exposure, intensity, and the temporal pattern of malaria transmission. 2. Evaluate the relationship between immunity to these Ags and resistance to re-infection in the two endemic areas. 3. Determine whether elimination of liver-stage P. falciparum through primaquine prophylaxis effects T or B cell responses to LSA1 and/or SSP2/TRAP and CSP antigenic peptides. 4. Assess the effect of prolonged elimination of liver-stage parasites with primaquine on resistance to reinfection. These field-based studies will provide insight into how immunologic boosting through natural infection influences resistance to re-infection and T and B cell immunity to vaccine candidate antigens.
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