Abstract. In support of ongoing immunologic studies on immunity to Plasmodium falciparum, demographic, entomologic, parasitologic, and clinical studies were conducted in two Cameroonian villages located 3 km apart. Simbok (population ϭ 907) has pools of water present year round that provide breeding sites for Anopheles gambiae, whereas Etoa (population ϭ 485) has swampy areas that dry up annually in which A. funestus breed. Results showed that individuals in Simbok receive an estimated 1.9 and 1.2 infectious bites per night in the wet and dry season, respectively, whereas individuals in Etoa receive 2.4 and 0.4 infectious bites per night, respectively. Although transmission patterns differ, the rate of acquisition of immunity to malaria appears to be similar in both villages. A prevalence of 50-75% was found in children Ͻ 10 years old, variable levels in children 11-15 years old, and 31% in adults. Thus, as reported in other parts of Africa, individuals exposed to continuous transmission of P. falciparum slowly acquired significant, but not complete, immunity.

The Plasmodium falciparum rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) are candidate antigens for a subunit malaria vaccine. The design of the study, which looks at the acquisition of immunity to malaria from childhood to old age, has allowed us to document the interaction of HLA and age on levels of antibody to specific malarial antigens. Antibodies reach maximum levels to RAP1 after the age of 15 but to RAP2 only after the age of 30. The effect of HLA-DRB1 and -DQB1 and age on levels of antibody to rRAP1 and rRAP2 was analyzed with a multiple regression model in which all HLA alleles and age were independent variables. DQB1*0301 and -*03032 showed an age-dependent association with levels of antibody to rRAP1, being significant in children 5 to 15 years (P < 0.001) but not in individuals over 15 years of age. DRB1*03011 showed an age-dependent association with antibody levels to rRAP2; however, this association was in adults over the age of 30 years (P < 0.01) but not in individuals under the age of 30 years. No associations were detected between DRB1 alleles and RAP1 antibody levels or between DQB1 alleles and RAP2 antibody levels. Thus, not only the HLA allele but also the age at which an interaction is manifested varies for different malarial antigens. The interaction may influence either the rate of acquisition of antibody or the final level of antibody acquired by adults.The rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) form a low-molecular-mass complex located in the rhoptries of Plasmodium falciparum (5, 9). The rhoptries are a pair of organelles at the apical end of the parasite that are involved in the invasion of erythrocytes; thus, molecules in the rhoptries were among the first components identified as potential candidates for a subunit vaccine. Subsequent studies have borne out this potential. Monoclonal antibodies (MAbs) directed against rhoptry-associated proteins have been shown to provide substantial inhibition of parasite invasion in vitro (7,17,19,22,29,37). In addition, protein preparations containing both RAP1 and RAP2 have been used to immunize Saimiri monkeys. In these studies, the immunized monkeys developed a lower peak parasitemia than nonimmunized controls and were protected from subsequent lethal blood-stage challenge with P. falciparum (9,30,32,34) in a way similar to the protection acquired by immunization with whole merozoite (27,39,46). Two rhoptry-associated proteins, RAP1 and RAP2, have been sequenced (20,36). Unlike many other P. falciparum antigens, RAP1 and RAP2 exhibit a high degree of sequence similarity among P. falciparum isolates. Isolates from Honduras,