Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP1(19)) induces protective immunity to blood stage malaria infection in mice

Variable protection against malaria blood-stage infection has been demonstr ated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP1(19)) using CFA/IFA and other adjuvants. Here we show that intranasal immunizati on of BALB/C mice with yeast expressed Plasmodium yoelii MSP119 plus a mixt ure of native and recombinant cholera toxin B subunit, could induce serum M SP1(19)-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunizati on led to protection following challenge (peak parasitaemia <1%) in mice wi th the highest MSP1(19)-specific titre (greater than or equal to 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%-1% was foll owed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02 %. In unprotected mice, antibody levels rose, then fell, following the dete ction of parasites in the peripheral blood. CD4(+) T cell-depletion abrogat ed the ability of the mice to boost their antibody response following chall enge. These data demonstrate the potential for intranasal immunization with MSP1(19) to protect against malaria.