POLYMORPHISM OF A HIGH MOLECULAR WEIGHT SCHIZONT ANTIGEN OF THE HUMAN MALARIA PARASITE

Clinical manifestations of malaria are associated with repeated cycles of multiplication of the parasite in the blood, and any prospective immunopr0phylaxis needs effectively to control the blood phase of the infection. Present attempts (1-10) to identify parasite antigens of potential value in vaccination against asexual blood stages of the human parasite Plasmodium falciparum have implicated a number of different parasite polypeptides. However, experimentally induced immunity against the blood forms of P. falciparum is known to have a significant isolate-specific component (1 1-16), indicating intraspecies antigenic diversity in one or several of the relevant protective antigen(s ) . Furthermore, in endemic areas, individuals naturally exposed to the infection suffer repeated parasitemias and clinical attacks of the disease before any degree of immunity is acquired (17, 18). The reasons for such a slow and gradual development of immunity are unknown but the pattern is consistent with the existence of a variety of antigenically distinct parasite strains to which a human host may need to be exposed before he acquires cumulative immunity against the majority of the diverse strains present in his environment. It is therefore crucial to research aimed at the development of widely applicable vaccine that the degree of antigenic diversity in defined parasite antigens is elucidated. Moreover, most immunological research on malaria has been carried out with a limited number of antigenicaily poorly defined P. falciparum isolates and it is not known how far such isolates are representative of wild parasite populations in endemic areas. Thus there is a need for a system of immunological classifications of the parasite in order to understand how experimental results obtained in the laboratory may relate to the situation in the field. Recently, we have used a panel of strain-specific monoclonal antibodies (mAb) ~ to demonstrate that the species P. falciparum consists of a number of antigenically diverse strains. Some of these strains may have a world-wide distribution (19, This work was supported by a grant from The Wellcome Trust. Address correspondence to J. McBride. 1 Abbreviations used in this paper: BSA, bovine serum albumin; DMSO, dimethyl sulfoxide; IFA, indirect immunofluorescence assay; mAb, monoclonal antibody; NP-40, Nonidet P-40; PBS, phosphate-buffered saline; PMSF, phenylmethylsulfonyl fluoride; PPO, 2,5,-dipbenyloxazole; PSA, polymorphic schizont antigen; SDS-PAGE, sodium dodecyl sulphate-polyacrylarnide gel electrophoresis; TCLK, tosyI-L-lysine chloromethyl ketone.