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Infection and Immunity, March 2000, p. 1418-1427, Vol. 68, No. 3
0019-9567/00/$04.00+0

Vaccine Efficacy of Recombinant Plasmodium falciparum Merozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -Rechallenged Aotus vociferans Monkeys

Andrea F. Egan,1 Michael J. Blackman,2 and David C. Kaslow1,*

Malaria Vaccines Section and Malaria Vaccine Development Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 and Division of Parasitology, National Institute for Medical Research, London, United Kingdom2

Received 22 June 1999/Returned for modification 18 August 1999/Accepted 2 November 1999

Protection against a lethal challenge infection of Plasmodium falciparum was elicited in malaria-naive Aotus vociferans monkeys by vaccination with the C terminus 19-kDa protein of the major merozoite surface protein (MSP-119) fused to tetanus toxoid universal T-cell epitopes P30 and P2. Three of four monkeys were protected against a 104-parasite challenge. Four monkeys were challenged with 105 parasites; one self-cured the infection, two were protected against high parasitemia (<2%) but were treated for severe anemia (hematocrit of <25%), and the fourth was not protected. In this model system, anemia appears to be a manifestation of incomplete protection (prolonged low-level parasitemia). Enzyme-linked immunosorbent assay (ELISA) antibody titers correlated with protection. Antibodies from some protected monkeys inhibited secondary processing of MSP-142 to MSP-133 and MSP-119. To mimic the repeated reinfections seen in regions where malaria is endemic, a second malaria parasite challenge was administered 4 months later. All P30P2MSP-119-vaccinated monkeys were protected; thus, a single challenge infection may underestimate vaccine efficacy. ELISA antibody titers correlated with protection against a second infection but had decreased compared to the first challenge. As most target populations for asexual blood-stage malaria vaccines will have been exposed to malaria parasites, a malaria parasite-exposed monkey was vaccinated with P30P2MSP-119. This monkey was completely protected, while a malaria parasite-naive P30P2MSP-119-vaccinated monkey self-cured a low-grade parasitemia. Prior malaria parasite infection primed the production of anti-native MSP-119 antibodies, which were boosted by vaccination with recombinant P30P2MSP-119. Preliminary data suggest that immunogenicity studies of vaccines designed for malaria parasite-exposed populations should also be conducted in malaria parasite-exposed subjects.

* Corresponding author. Present mailing address: Virus and Cell Biology, Merck Research Labs, WP 16-225, West Point, PA 19486. Phone: (215) 652-3929. Fax: (215) 652-0994. E-mail: david_kaslow{at}merck.com.

Infection and Immunity, March 2000, p. 1418-1427, Vol. 68, No. 3
0019-9567/00/$04.00+0


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