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Clinical and Vaccine Immunology, April 2007, p. 342-347, Vol. 14, No. 4
1071-412X/07/$08.00+0     doi:10.1128/CVI.00397-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment of Plasmodium yoelii Merozoite Surface Protein 1 in Mice

Department of Microbiology, Faculty of Public Health,¹ Department of Microbiology and Immunology, Faculty of Tropical Medicine,² Department of Parasitology, Faculty of Public Health, Mahidol University, Bangkok, Thailand,³ Department of Immunology and Medicine, U.S. Armed Forces Research Institute of Medical Science, Bangkok, Thailand⁴

Received 20 October 2006/ Returned for modification 22 December 2006/ Accepted 8 February 2007

Merozoite surface protein 1 (MSP1) is the major protein on the surface of the plasmodial merozoite, and its carboxy terminus, the 19-kDa fragment (MSP1₁₉), is highly conserved and effective in induction of a protective immune response against malaria parasite infection in mice and monkeys. However, the duration of the immune response has not been elucidated. As such, we immunized BALB/c mice with a standard four-dose injection of recombinant Plasmodium yoelii MSP1₁₉ formulated with Montanide ISA51 and CpG oligodeoxynucleotide (ODN) and monitored the MSP1₁₉-specific antibody levels for up to 12 months. The antibody titers persisted constantly over the period of time without significant waning, in contrast to the antibody levels induced by immunization with Freund's adjuvant, where the antibody levels gradually declined to significantly lower levels 12 months after immunization. Investigation of immunoglobulin G (IgG) subclass longevity revealed that only the IgG1 antibody level (Th2 type-driven response) decreased significantly by 6 months, while the IgG2a antibody level (Th1 type-driven response) did not change over the 12 months after immunization, but the boosting effect was seen in the IgG1 antibody responses but not in the IgG2a antibody responses. After challenge infection, all immunized mice survived with negligibly patent parasitemia. These findings suggest that protective immune responses to MSP1₁₉ following immunization using oil-based Montanide ISA51 and CpG ODN as an adjuvant are very long-lasting and encourage clinical trials for malaria vaccine development.

Published ahead of print on 21 February 2007.