RESUMO
Antibody responses to malaria invasion ligands and proteins on the merozoite surface have been shown to interfere with red cell invasion and correlate with immunity to malaria. The current study is the first to characterize the antibody responses to EBA-140 and EBA-181, Plasmodium falciparum invasion ligands implicated in the alternative pathways of invasion, in age-matched populations of individuals living in endemic areas in both Brazil and Cameroon. Antibody responses to the proteins screened were different between populations. The African individuals reacted strongly with most fragments of these two EBAs, while the majority of the individuals from Mato Grosso, Brazil, reacted weakly and those from the Amazon had elevated responses to these EBA proteins. When compared with the responses against MSP-1(19) and EBA-175, it appeared that the Brazilian population has a variable ability to recognize P. falciparum invasion ligand proteins and that these responses are distinct from the African population.
Assuntos
Anticorpos Antiprotozoários/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/imunologia , Adulto , Distribuição por Idade , Animais , Brasil/epidemiologia , Camarões/epidemiologia , Doenças Endêmicas , Regulação da Expressão Gênica , Humanos , Plasmodium falciparum/imunologia , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes/imunologiaAssuntos
Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/genética , Sequência de Aminoácidos , Animais , Brasil , Eritrócitos/parasitologia , Variação Genética , Ligantes , Malária Falciparum/parasitologia , Dados de Sequência Molecular , Fenótipo , Plasmodium falciparum/isolamento & purificação , Polimorfismo Genético , Virulência/genéticaRESUMO
The invasion of red blood cells (RBCs) by Plasmodium falciparum is dependent on multiple molecular interactions between erythrocyte receptors and parasite ligands. Invasion studies using culture-adapted parasite strains have indicated significant receptor heterogeneity. It is not known whether this heterogeneity reflects the parasite invasion arsenal in the field. We have studied the invasion phenotypes of 14 distinct field isolates from the Legal Amazon areas of Brazil by using erythrocyte invasion assays to investigate invasion into normal, enzyme-treated, and clinical-mutant RBCs. Analysis of these isolates revealed four distinct invasion profiles. Using En(a-) cells to get an unequivocal estimate of the use of glycophorin A (GPA) as a receptor, we found that the 175-kDa erythrocyte-binding antigen (EBA-175)/GPA pathway was used by a minority of the parasite isolates studied. Although polymorphism of region II domains at specific amino acid positions in both EBA-140 and EBA-181 was found in these field isolates, this did not correlate with invasion profiles and thus receptor selectivity. These studies have further confirmed the existence of a significant diversity of invasion pathways in nature and suggest that additional parasite ligands will have to be targeted to devise global vaccines that will work in the field.