Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSASM) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSAUM). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSAUM to in vitro–selected sublines expressing VSASM to identify PfEMP1 responsible for the VSASM phenotype. Expression of VSASM was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.

The humoral immune response against synthetic peptides of two Plasmodium falciparum blood-stage antigens, Pf155/ring-infected erythrocyte surface antigen (RESA) (EENV) 6 and Pf332 (SVTEEIAEEDK) 2 , in individuals belonging to three sympatric ethnic groups (Mossi, Rimaibe, and Fulani) living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso were examined. The Mossi and Rimaibe are Sudanese Negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists partly settled and characterized by non-Negroid features of possible Caucasoid origin. A total of 764 subjects (311 Mossi, 273 Rimaibe, and 180 Fulani) were tested. A lower P. falciparum prevalence was observed in the Fulani of all age groups. The serologic results clearly indicate the existence of interethnic differences in the capacity to respond to these two P. falciparum antigens. The Mossi and Rimaibe showed similar responses, whereas the Fulani displayed consistently higher prevalences and levels of antibodies against both epitopes tested. The anti-(EENV) 6 and anti-(SVTEEIAEEDK) 2 seroprevalences were 29.9% and 38.9% in Mossi, 29.7% and 39.2% in Rimaibe, 86.1% and 76.1% in Fulani (all P values of Fulani-Mossi and Fulani-Rimaibe comparisons K 0.001). Anti-RESA and anti-Pf332 antibody levels were approximately 65% (P K 0.001) and 45% (P K 0.001), respectively, higher in seropositive Fulani than in seropositive Mossi and Rimaibe, who showed very similar values. The observed differences cannot be explained in terms of interethnic heterogeneity of malaria exposure since these communities have lived in the same area for more than 30 years and the P. falciparum inoculation rate, measured during two consecutive years, was substantially uniform for the three ethnic groups. The possibility of remarkable heterogeneities in the capacity to mount immune responses against P. falciparum antigens among populations with different genetic backgrounds must be taken into account in the development of anti-malaria vaccines.

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...

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