Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages

Abstract

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

“…Merozoite surface protein-1, the first antigen discovered on the surface of erythrocytic stage merozoites, is also expressed in all generations of merozoites, including those released at the end of hepatic schizogony [48]. The C-terminal portion of the MSP-1 is the target of protective immunity as suggested by epidemiological studies [49,50] and as demonstrated by the protection of Aotus monkeys against malaria challenge by immunization with 42-kDa C-terminal MSP-1 recombinant protein [51,52].…”

Reduced immunogenicity of DNA vaccine plasmids in mixtures

“…Immunofluorescence assays were carried out using air-dried P. falciparum sporozoites and air-dried parasitized erythrocytes. 13,14 …”

Vaccination with LivePlasmodium yoeliiBlood Stage Parasites under Chloroquine Cover Induces Cross-Stage Immunity against Malaria Liver Stage

“…Recent pan-genomic analyses of the proteomes and transcriptomes of the distinct parasite stages observed during the life cycle, have revealed that many Plasmodium proteins are expressed during different stages of the life cycle (11–18), and pertinently that in many cases these included Ags expressed by both pre-erythrocytic and erythrocytic parasites (19–26). This response has raised the possibility that some of these proteins could become the target of parasite-induced immune responses that would then lead to some degree of cross-stage immunity in the mammalian host (24, 25).…”