Plasmodium: Immunization with carboxyl-terminal regions of MSP-1 protects against homologous but not heterologous blood-stage parasite challenge

A leading candidate for a vaccine targeted at the erythrocytic stages of pl asmodial parasite development is the merozoite surface protein-1 (MSP-1). W e have previously shown that the carboxyl-terminal region of MSP-1 derived from Plasmodium yoelii yoelii 17XL, expressed as a fusion protein with glut athione S-transferase (GST-PYC2), can immunize mice against an otherwise le thal homologous challenge infection. This protection has been shown to be p redominantly mediated by antibodies. We report here on the efficacy of immu nization with MSP-1 carboxyl regions when the challenge is a heterologous r odent parasite species. The course of parasitemia was not altered in mice i mmunized with GST-PYC2 and challenged with 10(4) heterologous Plasmodium ch abaudi adami parasites, as both control and immunized mice developed infect ions that peaked at day 7 and then rapidly declined. Similarly, mice immuni zed with GST-PYC2 and challenged with 10(5) Plasmodium berghei ANKA parasit es displayed virulence similar to that seen in infection control mice. The homologous region of the P. chabaudi adami MSP-1 gene was similarly express ed as a fusion protein with GST. Mice immunized with GST-PCC2 and challenge d with 10(4) parasites showed significant protection against homologous P. chabaudi adami infection but no protection whatsoever against heterologous P. yoelii yoelii 17XL infection. These in vivo results correlate with the o bservation that sera generated by immunization with the carboxyl region of MSP-1 recognizes this protein from homologous, but not heterologous, radiol abeled parasite protein preparations. (C) 1999 Academic Press.