Protective Immune Responses to the 42-Kilodalton (kDa) Region of Plasmodium yoelii Merozoite Surface Protein 1 Are Induced by the C-Terminal 19-kDa Region but Not by the Adjacent 33-kDa Region

Abstract

ABSTRACT Vaccination of mice with the 42-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP1 42 ) or its 19-kDa C-terminal processing product (MSP1 19 ) can elicit protective antibody responses in mice. To investigate if the 33-kDa N-terminal fragment (MSP1 33 ) of MSP1 42 also induces protection, the gene segment encoding MSP1 33 was expressed as a glutathione S -transferase (GST) fusion protein. C57BL/6 and BALB/c mice were immunized with GST-MSP1 33 and subsequently challenged with the lethal P. yoelii YM blood stage parasite. GST-MSP1 33 failed to induce protection, and all mice developed patent parasitemia at a level similar to that in naive or control (GST-immunized) mice; mice immunized with GST-MSP1 19 were protected, as has been shown previously. Specific prechallenge immunoglobulin G (IgG) antibody responses to MSP1 were analyzed by enzyme-linked immunosorbent assay and immunofluorescence. Despite being unprotected, several mice immunized with MSP1 33 had antibody titers (of all IgG subclasses) that were comparable to or higher than those in mice that were protected following immunization with MSP1 19 . The finding that P. yoelii MSP1 33 elicits strong but nonprotective antibody responses may have implications for the design of vaccines for humans based on Plasmodium falciparum or Plasmodium vivax MSP1 42 .