Antibody responses to the repetitivePlasmodium falciparumantigen Pf332 in humans naturally primed to the parasite

Abstract

SUMMARYAntibodies to the degenerate repeats of EB200, a part of the Plasmodium falciparum antigen Pf332, are protective in monkeys. To analyse the prevalence, magnitude and specificity of antibodies to EB200 in malaria-exposed humans, the IgG antibody reactivity with recombinant EB200 protein as well as with crude malaria antigen was determined in Senegalese donors (n = 100; 4-87 years). Antibody reactivity with EB200 was low or absent in children below 15 years but was prevalent and significantly higher in older donors. In comparison, all individuals displayed reactivity with a crude malaria antigen preparation, which also increased with age. The reactivity with the crude malaria antigen was correlated to the reactivity with EB200, suggesting that the low levels of IgG to EB200 found in some adult donors reflected a limited degree of recent exposure to parasites rather than a selective nonresponsiveness to Pf332. Comparison of serological and clinical data showed that high levels of antibodies to crude malaria antigen and to EB200 were predictive of fewer future clinical attacks of malaria. A reactivity pattern very similar to that found in Senegalese donors was observed in Liberian adults where 80% of the sera showed reactivity with EB200 and all peptides were recognized by between 60 and 100% of the donors. This strong reactivity with EB200-derived overlapping peptides suggests that the epitopes in EB200, to a large extent, are linear. In the light of previous data on the parasite neutralizing capacity of antibodies to Pf332, the present results emphasize the potential interest of Pf332-derived sequences for inclusion in a subunit vaccine against P. falciparum malaria.

A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray

“…Antigen 332 is expressed in trophozoites and translocated to the erythrocyte membrane during the schizont stage (29). Abs against Pf332 have been shown to inhibit parasite grown in vitro (30) and have been associated with decreased parasitemia (31) and decreased malaria risk (32) in field studies.…”

Infection withPlasmodium bergheiBoosts Antibody Responses Primed by a DNA Vaccine Encoding Gametocyte Antigen Pbs48/45

“…It is well known that serum from people who are naturally exposed to malaria or from animals infected with malaria parasites can recognize several of the leading vaccine antigens (2,31). However, few studies exist in humans (40) or in animal FIG.…”

Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite

“…The Plasmodium falciparum asexual blood‐stage antigen Pf332 is expressed in trophozoites, and the antigen is translocated to the surface of mature schizonts [1,2]. Antibodies reactive with Pf332 have been shown to be parasite neutralizing in P. falciparum in vitro cultures [3], and they have also been associated with lower parasitaemia [4] and lower numbers of malaria attacks [5], observations forming the basis for considering the antigen a vaccine candidate. Previous analyses of Pf332 have focused on epitopes in the glutamic acid (Glu)‐rich repeat region of the antigen, and in particular on EB200, a 157‐amino‐acid fragment in the central part of Pf332 [6].…”

“…Previous analyses of Pf332 have focused on epitopes in the glutamic acid (Glu)‐rich repeat region of the antigen, and in particular on EB200, a 157‐amino‐acid fragment in the central part of Pf332 [6]. EB200 appears to be highly immunogenic in humans, as indicated by the high prevalence of antibody reactivity to it in individuals exposed to malaria [5,7]. However, as antibodies reactive with EB200 are potentially cross‐reactive with other Glu‐rich P. falciparum antigens [8,9], it is difficult to identify the true target antigen for the antibodies.…”