Malaria, caused by Plasmodium falciparum, is a major health problem, especially for young children and pregnant women living in Cameroon. Multi-drug resistant strains of P. falciparum are present throughout Central Africa making the development of a vaccine for malaria a necessity. Unfortunately, it is unclear what types and levels of acquired immune responses need to be induced for a vaccine to be successful, or if a vaccine will be equally effective in pregnant women and young children since they have different immunologic backgrounds. The goal of our project is to provide basic information about the acquisition of immunity that will help direct the development of a successful vaccine for P. falciparum. The proposed studies will take place in Yaounde and in a rural village, Simbok, located 5 miles west of the city. Project #1 seeks to identify changes within the placenta due to malaria infection that lead to spontaneous abortions, stillborn infants, and premature deliveries. Studies will focus on changes within the placenta that may lead to altered fetal development, including levels of tumor necrosis factor (TNF), aberrant expression of HLA antigens on syncytiotrophoblasts, and strains of parasites that differ in virulence. Project #2 proposes to define immunologic changes that take place in infants during their first year of life. Techniques in immunology and molecular biology will be used to determine when an infant first becomes infected and how primary infection influences anti-parasite immune responses. Project #3 studies children from 1 year of age through acquisition of malarial immunity. It specifically tests the hypothesis that young children primarily produce T cell responses to immunodominant, variant T cell epitopes which generate only short-term immunity, whereas adults respond to conserved, epitopes which induce long-term, protective immunity. It also test the hypothesis that the rate at which one develops immunity, as well as the type and specificity of immunity to P. falciparum, is influenced, in part, by the MHC haplotype of the individual. The three studies focus on antigens with vaccine potential, and should provide valuable information about the acquisition of immunity in Cameroonians.

U01AI035839

1994-07-01

2000-03-31