Linkage of exogenous T-cell epitopes to the 19-kilodalton region of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) can enhance protective immunity against malaria and modulate the immunoglobulin subclass response to MSP1(19)

The degree of protection against Plasmodium yoelii asexual blood stages ind uced by immunization of mice with the 19-kDa region of merozoite surface pr otein 1 (MSP1(19)) is H-2 dependent. As a strategy to improve the protectio n, mouse strains with disparate H-2 haplotypes were immunized with glutathi one S-transferase (GST)-MSP1(19) proteins including either a universal T-ce ll epitope from tetanus toxin (P2) or an I-A(k)-restricted T-cell epitope ( P8) from Plasmodium falciparum Pf332. In H-2(k) mice which are poorly prote cted following immunization with GST-MSP1(19), GST-P2-MSP1(19) significantl y improved the protection. In mice partially (H-(2k/b)) or well protected b y GST-MSP1(19) (H-2(d) and H-2(b)), P2 did not further increase the protect ion. However, the protection of H-2(k/b) mite and to some extent H-2(k) mic e was improved by immunization with GST-P8-MSP1(19). The magnitudes of immu noglobulin G1 (IgG1) and IgG2a responses in mice immunized with the GST-MSP 1(19) variants correlated with low peak parasitemia, indicating a protectiv e capacity of these IgG subclasses. In H-2(k) mice immunized with GST-P2-MS P1(19), both IgG1 and IgG2a responses since significantly enhanced. The epi tope P2 appeared to have a general ability to modulate the IgG subclass res ponse since all four mouse strains displayed elevated IgG2a and/or IgG2b le vels after immunization with GST-P2-MSP1(19). In contrast, GST-P8-MSP1(19) induced a slight enhancement of IgG responses in H-2(k/b) and H-2(k) mice w ithout any major shift in IgG subclass patterns. The ability to improve the protective immunity elicited by P. yoelii MSP1(19) may have implications f or improvement of human vaccines based on P. falciparum MSP1(19).