Interethnic differences in the humoral response to non-repetitive regions of the Plasmodium falciparum circumsporozoite protein.

Abstract

Abstract. We analyzed the humoral immune response to the amino-(amino acids 22-125) and carboxy-terminal (amino acids 289-390) non-repetitive domains of the Plasmodium falciparum circumsporozoite protein (Pf CSP) in individuals belonging to three west African ethnic groups (the Fulani, Mossi, and Rimaibé) living in the same conditions of hyperendemic transmission in a Sudan savanna area of Burkina Faso. Previous surveys conducted in the same area showed obvious interethnic differences in the susceptibility and immune reactivity to malaria, with the Fulani showing lower infection and disease rates and higher humoral responses to various P. falciparum antigens than sympatric ethnic groups. A total of 764 subjects (311 Mossi, 273 Rimaibé, and 180 Fulani) of all age classes were tested. The total mean Ϯ SE anti-(CSPf-N-term) and anti-(CSPf-C-term) seroprevalences were 65.6 Ϯ 1.7% and 57.0 Ϯ 1.8%, respectively. These seroprevalences were lower than that recorded in the same sample for the central (NANP) 40 repetitive domain (88.3 Ϯ 1.2%). As previously reported for other P. falciparum antigens (Pf CSP-(NANP) 40 , thrombospondin-related anonymous protein, merozoite surface protein-1, Pf 155-ring-infected eryhtrocyte surface antigen, and Pf 332), in spite of similar exposure to malaria, the Fulani showed higher immune reactivity than sympatric populations for both antigens tested. Our results confirm the presence of B cell epitopes in the non-repetitive regions of the Pf CSP; moreover a further evidence of interethnic differences in the capacity to mount humoral responses against P. falciparum malaria was obtained. The assessment of the biological basis of interethnic heterogeneities in the susceptibility and in the humoral immune responses to malaria appears relevant in the development of anti-malaria vaccines.The circumsporozoite protein (CSP) is considered to be the major surface antigen of malaria sporozoites. The main structural and antigenic properties of CSP are identical in all Plasmodium species; the molecule contains a species-specific repetitive domain encompassing about 40% of the primary structure of the protein, which corresponds to the B cell immunodominant epitope.1 In Plasmodium falciparum, the central domain contains about 40 repeats of the tetrapeptide NANP plus 3-4 NVDP repeats. The central domain is flanked on both sides by sequences containing conserved regions in different Plasmodium species. 2 The carboxy-terminal conserved region (region II) bears a striking homology to a cell adhesion domain of thrombospondin 3,4 and to regions of several other adhesive proteins. [5][6][7][8] The involvement of CSP in the invasion of sporozoites into hepatocytes has been shown by Cerami and others. 9 The flanking non-repeat regions of CSP contain several epitopes recognized not only by antibodies, 10-17 but also by CD4 ϩ T helper cells 18-20 and CD8 ϩ cytotoxic T lymphocytes. [21][22][23][24] Vaccine candidates based on the immunodominant, repetitive domain of the P. falciparum CSP (Pf CSP) gave unsatisfactor...

Impact of Indoor Residual Spraying of Lambda-Cyhalothrin on Malaria Prevalence and Anemia in an Epidemic-Prone District of Muleba, North-Western Tanzania

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Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria

“…Despite similar exposure to malaria and comparable use of protective measures, the Fulani were less parasitized and less affected by the disease. This resistance was not associated to classic malaria resistance genes (4), and the analysis of the antibody response to P. falciparum antigens revealed higher immune reactivity in Fulani than in sympatric ethnic groups (1,5,6). The hypothesis of a stronger activation of the immune system in the Fulani is also suggested by the higher frequency in this group of the tropical splenomegaly syndrome (2,7) and by the higher humoral immune response to other pathogens (Schistosoma haematobium, hepatitis B, and cytomegalovirus).…”

“…IgG against P. falciparum CSP and MSP-1 19 were measured by ELISA as described (6). Data were compared by using the Kruskal-Wallis test.…”

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

“…The higher incidence of spleen enlargement in the Fulani might reflect a hyper immune reactivity of this secondary lymphoid organ (Bereczky et al, 2006;Vafa et al, 2009a;Alkadarou et al, 2013), a hypothesis supported by several studies which consistently show that the Fulani mount a more robust humoral immune response, as reflected by increased titers of anti-plasmodial antibodies (Modiano et al, 1998(Modiano et al, , 1999Bolad et al, 2005;Farouk et al, 2005a;Vafa et al, 2009a). The levels of malaria blood-stage antibodies anti-AMA1 and anti-MSP1 were significantly increased in Fulani, suggesting the higher specific humoral responses against AMA1 and MSP1 in this ethnic group (Dolo et al, 2012a).…”