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Induction of crossreactive antibodies against the Plasmodium falciparum variant protein.


ABSTRACT: The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surface of P. falciparum-parasitized erythrocytes (PE), plays a central role in naturally acquired immunity, although antibodies to PfEMP1 are predominantly variant specific. To overcome this major limitation for vaccine development, we immunized mice with three cysteine-rich interdomain 1 (CIDR1) domains of PfEMP1 that have the critical function of binding the PE to CD36 on endothelium and thus preventing spleen-dependent killing of the parasite. The immunizations consisted of different combinations of three CIDR1 encoded by DNA followed by recombinant protein boost. Immunizations with a single variant in a prime-boost regimen induced no or low cross-reactivity toward heterologous CIDR1; however, a broad range of crossreactivity was detected in mice that were immunized with all three variants simultaneously. The induced crossreactivity suggests that an anti-PfEMP1 vaccine may be possible.

SUBMITTER: Gratepanche S 

PROVIDER: S-EPMC240735 | biostudies-literature | 2003 Oct

REPOSITORIES: biostudies-literature

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Induction of crossreactive antibodies against the Plasmodium falciparum variant protein.

Gratepanche Sylvie S   Gamain Benoit B   Smith Joseph D JD   Robinson Bridget A BA   Saul Allan A   Miller Louis H LH  

Proceedings of the National Academy of Sciences of the United States of America 20031020 22


The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surface of P. falciparum-parasitized erythrocytes (PE), plays a central role in naturally acquired immunity, although antibodies to PfEMP1 are predominantly variant specific. To overcome this major limitation for vaccine development, we immunized mice with three cysteine-rich interdomain 1 (CIDR1) domains of PfEMP1 that have the critical function of binding the PE to CD36 on endothelium and thus pre  ...[more]

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