Humoral response to a carboxyl-terminal region of the merozoite surface protein-1 plays a predominant role in controlling blood-stage infection in rodent malaria.
The developmental stages of malaria parasites that infect E are responsible for the morbidity and mortality associated with this disease. One of the leading candidates for a blood-stage vaccine against malaria is a surface protein of merozoites, the infectious stages for E, designated merozoite surface protein-1 (MSP-1). The rodent malarial parasite Plasmodium yoelii yoelii (Py) has provided a model system for the study of this Ag, and previous studies from our laboratory had demonstrated that the carboxyl-terminal, cysteine-rich region of MSP-1, when expressed in a native configuration, could immunize mice against a normally lethal challenge infection with Py. We have now prepared a new fusion construct with the glutathione-S-transferase gene of Schistosoma japonicum joined to the carboxyl-terminal 11 kDa of Py MSP-1. This includes only the two epidermal growth factor-like domains of the MSP-1 protein. When expressed in recombinant Escherichia coli, the fusion protein induces a strong protective response in BALB/c mice as judged by the resistance of immunized animals to a virulent challenge infection. Moreover, we demonstrate that this resistance can be transferred passively by immune serum or by purified Ig, establishing a significant role for humoral immunity in protection. No role for CD4+ or CD8+ T cells could be identified in the first 12 days after challenge infection in immune mice selectively depleted of these cells; however, after this time, parasitemias gradually increased in mice depleted of CD4+ T cells, suggesting an active host response is necessary to completely eliminate the infection.
Daly
T M
TM
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19102, USA.
Long
C A
CA
D000818:Animals; D000913:Antibodies, Protozoan / Q000378:metabolism; D000917:Antibody Formation; D001483:Base Sequence; D004306:Dose-Response Relationship, Immunologic; D005982:Glutathione Transferase / Q000378:metabolism; D007116:Immunization, Passive / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D008212:Lymphocyte Depletion; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D020066:Merozoite Surface Protein 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase