Abstract
ABSTRACTProtection against a lethal challenge infection ofPlasmodium falciparumwas elicited in malaria-naiveAotus vociferansmonkeys 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 105parasites; 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-142to MSP-133and 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-119antibodies, 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.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 27, 2002, 6:03 a.m.) |
Deposited | 2 years, 4 months ago (April 23, 2023, 11:44 a.m.) |
Indexed | 4 months, 4 weeks ago (April 8, 2025, 6:58 p.m.) |
Issued | 25 years, 6 months ago (March 1, 2000) |
Published | 25 years, 6 months ago (March 1, 2000) |
Published Print | 25 years, 6 months ago (March 1, 2000) |
@article{Egan_2000, title={Vaccine Efficacy of RecombinantPlasmodium falciparumMerozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -RechallengedAotus vociferansMonkeys}, volume={68}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.68.3.1418-1427.2000}, DOI={10.1128/iai.68.3.1418-1427.2000}, number={3}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Egan, Andrea F. and Blackman, Michael J. and Kaslow, David C.}, editor={Mansfield, J. M.}, year={2000}, month=mar, pages={1418–1427} }