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

Abstract

ABSTRACT The degree of protection against Plasmodium yoelii asexual blood stages induced by immunization of mice with the 19-kDa region of merozoite surface protein 1 (MSP1 19 ) is H-2 dependent. As a strategy to improve the protection, mouse strains with disparate H-2 haplotypes were immunized with glutathione S -transferase (GST)–MSP1 19 proteins including either a universal T-cell 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 protected following immunization with GST-MSP1 19 , GST-P2-MSP1 19 significantly improved the protection. In mice partially (H-2 k/b ) or well protected by GST-MSP1 19 (H-2 d and H-2 b ), P2 did not further increase the protection. However, the protection of H-2 k/b mice and to some extent H-2 k mice was improved by immunization with GST-P8-MSP1 19 . The magnitudes of immunoglobulin G1 (IgG1) and IgG2a responses in mice immunized with the GST-MSP1 19 variants correlated with low peak parasitemia, indicating a protective capacity of these IgG subclasses. In H-2 k mice immunized with GST-P2-MSP1 19 , both IgG1 and IgG2a responses were significantly enhanced. The epitope P2 appeared to have a general ability to modulate the IgG subclass response since all four mouse strains displayed elevated IgG2a and/or IgG2b levels 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 without any major shift in IgG subclass patterns. The ability to improve the protective immunity elicited by P. yoelii MSP1 19 may have implications for improvement of human vaccines based on P. falciparum MSP1 19 .