Cross‐reactive cellular immune response to circumsporozoite proteins of Plasmodium vivax and P. falciparum in malaria‐exposed individuals

Abstract

Acquired immunity against the recombinant circumsporozoite protein of P. falciparum (rPfCS) or P. vivax (rPvCS) was studied in two malarious areas of the Brazilian Amazon. Cellular responsiveness, evaluated by proliferative assays, was detected in about 45% of individuals who had recovered from recent acute malaria infections. Peripheral blood mononuclear cells of individuals whose last malaria infection was by P. vivax responded more to the rCS proteins than those who had P. falciparum. Since in P. vivax infections hypnozoites in the liver retain CS antigen, this stage may have contributed to the increased cellular response. The unexpected result was that in primoinfections by P. falciparum or P. vivax the proliferative response did not correspond to the rPfCS and rPvCS, respectively. Furthermore, among the malaria-exposed individuals, there was a positive correlation between the intensity of the responses to the two rCS proteins. Our results suggest that cross-reactive epitopes exist in the CS protein of P. falciparum and P. vivax. In the areas studied, the frequency of antibodies against rPvCS and/or rPfCS ranged from 43% to 11%. Species-specific antibodies against the CS protein were detected in the primoinfected individuals. Some individuals living in the endemic area but with no clinical history of malaria were positive by serology (8%) or by in vitro proliferation (21%). However, antibodies and cellular responses against rCS were detected only in malaria-exposed individuals, since those living outside the endemic area were all negative.

Cellular responses to Plasmodium falciparum major surface antigens and their relationship to human activities associated with malaria transmission.

“…These data are consistent with our earlier studies that demonstrated that 30% of the individuals studied in the Brazilian Amazon had positive in vitro cellular responses to rPfCS. 18 The only other report concerning cellular responses to MSP-1 among Brazilians was to P.vivax. 28 The investigators used polypeptides representing the N-and C-terminal regions of the protein and showed PBMC stimulation ranging from 17% to 47% in the malaria-exposed group.…”

“…Peripheral blood mononuclear cells (PBMC) were isolated by Histopaque-1077 (Sigma) density gradient centrifugation as described elsewhere. 18 The PBMC were cultured in 96-well plates at a concentration of 1 ϫ 10 7 cells/ml in culture medium consisting of RPMI 1640 medium supplemented with 25 mM sodium bicarbonate, 25mM HEPES buffer, 3mM L-glutamine, 3% antibiotic-antimycotic mixture (300 U of penicillin, 300 g of streptomycin, 0.75 g of fungizone/ml), and 10% AB ؉ normal human serum. The recombinant proteins (rPfCS and rPfMSP-1) and yeast extract (control) were used at final concentrations of 10 g/ml;…”

“…In the areas studied, the frequency of antibodies ranged from 11% to 43%, while the cellular response was detected in approximately 45% of the individuals. 18 Moreover, in one area where the individuals were briefly exposed to a malaria outbreak, antibodies response against sporozoite and blood-stage antigens were detected up to seven years later. 19,20 The present study focus on the cellular response of individuals living within the same malaria-endemic area but belonging to two different social groups, i.e., gold-miners and farmers.…”

Prospective risk of morbidity in relation to malaria infection in an area of high endemicity of multiple species of Plasmodium.

“…3 This may in part be due to immunologically cross-reactive epitopes between P. falciparum and P. vivax. 4 However, there was no negative correlation for the P. falciparum-P. malariae, 3 and longitudinal studies indicate that malarial parasites can also favourably affect the host environment for other species. 5,6 Summarizing the literature available in 1988, Richie 1 argued that suppression of one species by another could be a result of competition for nutrients or for host cells, or of an immune-mediated ceiling to parasite density.…”

Low cellular response in vitro among subjects with long-term exposure to malaria transmission in Brazilian endemic areas.

“…7 Parallel tests of cellular responsiveness to P. falciparum and P. vivax recombinant CS (rCS) proteins, performed in areas where both parasites are transmitted, showed an overall positive rate of 45% in subjects recovering from acute malaria infection. 8 Although approximately half the people exposed to malaria in areas where transmission is low and unstable have T cells that recognize CS epitopes, these previous studies focused on subjects exposed for short periods of time, ranging from a few months to a few years. The mass migration of settlers to gold-rich areas or governmental agricultural settlement projects in the Amazon during the 1970s 9 meant that distinct groups are now exposed to malaria over decades.…”