Absolute requirement for an active immune response involving B cells and Th cells in immunity to Plasmodium yoelii passively acquired with antibodiesto the 19-kDa carboxyl-terminal fragment of merozoite surface protein-1

Vaccination of mice with the leading malaria vaccine candidate homologue, t he 19-kDa carboxyl terminus of merozoite surface protein-1 (MSP1(19)), resu lts in sterile immunity to Plasmodium yoelii, with no parasites detected in blood. Although such immunity depends upon high titer Abs at challenge, hi gh doses of immune sera transferred into naive mice reduce parasitemia (and protect from death) but do not result in a similar degree of protection (w ith most mice experiencing high peak parasitemias); this finding suggests t hat ongoing parasite-specific immune responses postchallenge are essential. We analyzed this postchallenge response by transferring Abs into manipulat ed but malaria-naive mice and observed that Abs cannot protect SCID, nude, CD4(+) T cell-depleted, or B cell knockout mice, with all mice dying. Thus, in addition to the Abs that develop following MSP1(19) vaccination, a cont inuing active immune response postchallenge is required for protection. MSP 1(19)-specific Abs can adoptively transfer protection to strains of mice th at are not protected following vaccination with MSP1(19), suggesting that t he Ags targeted by the immune response postchallenge include Ags apart from MSP1(19). These data have important implications for the development of a human malaria vaccine.