Recombinant Mycobacterium bovis bacillus Calmette-Guérin secreting merozoite surface protein 1 (MSP1) induces protection against rodent malaria parasite infection depending on MSP1-stimulated interferon gamma and parasite-specific antibodies.
The merozoite surface protein 1 (MSP1) has emerged as a leading malaria vaccine candidate at the erythrocytic stage. Recombinant bacillus Calmette-Guérin (rBCG), which expressed a COOH-terminal 15-kD fragment of MSP1 of Plasmodium yoelii (MSP1-15) as a fusion protein with a secretory protein of Mycobacterium kansasii, was constructed. Immunization of mice with this rBCG induced a higher degree of protection against blood-stage parasite infection than with recombinant MSP1-15 in the RIBI adjuvant (RIBI ImmunoChem Research, Inc., Hamilton, MT) or incomplete Freund's adjuvant systems. We studied the mechanism of protection induced by MSP1-15, and found that interferon (IFN)-gamma had a major role in protection in all adjuvant systems we examined. Mice that produced low amounts of MSP1-15 stimulated IFN-gamma and could not control parasite infection. The antibody against MSP1-15 did not play a major role in protection in this system. After parasite infection, immunoglobulin G2a antibodies, which had been produced by IFN-gamma stimulation, were induced and subsequently played an important role in eradicating parasites. Thus, both cellular and humoral immune responses were essential for protection from malaria disease. These data revealed that BCG is a powerful adjuvant to induce such a protective immune response against malaria parasites.
Matsumoto
S
S
School of Dentistry, Nagasaki University, Japan.
Yukitake
H
H
Kanbara
H
H
Yamada
T
T
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000502:physiology; D000918:Antibody Specificity; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D020066:Merozoite Surface Protein 1; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019909:Mycobacterium kansasii / Q000235:genetics; D009609:Nitrous Oxide / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology*; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D001500:BCG Vaccine; D007106:Immune Sera; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D007371:Interferon-gamma; D009609:Nitrous Oxide