The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/9/845/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 5, September 7, 1998 845-854

Articles

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

Sohkichi Matsumoto*, Hideharu Yukitake*, Hiroji Kanbara{ddagger}, and Takeshi Yamada*

From the * School of Dentistry, Nagasaki University, Nagasaki 852-8588, Japan; and the {ddagger} Department of Protozoology, Institute of Tropical Medicine, Nagasaki 852-8588, Japan

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.

Key Words: malaria vaccine • recombinant bacillus Calmette-Guérin • cytokine • protection • secretion system

Address correspondence to Takeshi Yamada, Nagasaki University, School of Dentistry, Sakamoto 1-7-1, Nagasaki 852-8588, Japan. Phone: 181-95-849-7649; Fax: 181-95-849-7650; E-mail: f 0338{at}cc.nagasaki-u.ac.jp

Abbreviations used: BBS, borate-buffered saline; BCG, bacillus Calmette-Guérin; CF, culture filtrates; D-NMMA, N G-monomethyl- D-arginine; GST, glutathione S-transferase; HSBBS, BBS containing 0.5 M NaCl; {alpha}-k, {alpha} antigen of Mycobacterium kansasii; L-NMMA, N G-monomethyl-L-arginine; MBP, maltose binding protein; MSP1, merozoite surface protein 1; MSP1-15, COOH-terminal fragment of MSP1 from Plasmodium yoelii 17XL; MSP1-19, COOH-terminal 19-kD fragment of MSP1 from Plasmodium falciparum; NO, nitric oxide; PAb, polyclonal antibody; PBS-T80, PBS containing 0.1% Tween 80; RAS, RIBI adjuvant system; rBCG, recombinant BCG clone; rBCGMSP1-15, rBCG secreting {alpha}-k–MSP1-15.


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