Monoclonal Antibodies Binding to Malarial Merozoite Surface Protein 1 Protect in vivo Against Plasmodium yoelii Infection

Spencer Valero, Lilian Maritza (1997). Monoclonal Antibodies Binding to Malarial Merozoite Surface Protein 1 Protect in vivo Against Plasmodium yoelii Infection. PhD thesis The Open University.

Abstract

The malarial merozoite invades the erythrocyte and develops within the host cell. One of the most important and well studied parasite surface proteins at this stage of the life cycle is merozoite surface protein-1 (MSP-1). Plasmodium falciparum MSP-1 undergoes proteolytic processing into several fragments, of which only the carboxyl-terminal 19 kDa fragment (MSP-119) remains on the merozoite surface during invasion of a new erythrocyte. To study the importance of antibodies to the 19 kDa fragment of Plasmodium yoelii MSP-1 in providing protective immunity against infection, MSP-1-specific monoclonal antibodies were produced and characterised. Six antibodies were studied in detail. When naïve mice were passively immunised with these antibodies and then challenged with P. yoelii YM; which is a virulent and lethal parasite line, four of the antibodies showed a protective effect, reducing the level of parasitacmia and increasing host survival. There was some correlation between antibody subclass and protection. The epitopes for the antibodies were located on MSP-1, two antibodies bound to a recombinant protein comprised of the whole of MSP-119, and two others bound to a smaller sub-domain of it. These antibodies also recognised a similar recombinant protein from P. yoelii 265 BY ; this cross-reaction occurred despite quite extensive sequence differences between the two polypeptides. Two other MSP-1 specific antibodies did not recognise recombinant MSP-119, one bound to an epitope in the protein sequence adjacent to MSP-119 and the second recognised a larger structure that included MSP-119. This panel of biologically active antibodies enables the mechanisms of antibody inhibition of erythrocyte invasion to be studied in detail.

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