Affiliation:
1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract
Vaccination with native full-length merozoite surface protein 1 (MSP1) or with recombinant C-terminal peptides protects mice against lethal challenge with virulent malaria parasites. To determine whether other regions of MSP1 can also induce protection, Plasmodium yoelii MSP1 was divided into four separate regions. Each was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The N-terminal fragment began after the cleavage site for the signal sequence and ended in the region comparable to the cleavage site for the C terminus of the 82-kDa peptide of Plasmodium falciparum. This expressed protein was 30 kDa smaller than the predicted peptide. One peptide from the middle region was produced, and the C terminus consisted of a 42-kDa fragment corresponding to the analogous peptide of P. falciparum and a 19-kDa fragment that extended 37 amino acids in the amino-terminal direction beyond the probable cleavage site. To test protection of mice against lethal P. yoelii challenge, three mouse strains (CAF1, BALB/c, and A/J) were vaccinated with each of the four recombinant proteins of MSP1. Mice vaccinated with the C-terminal 19-kDa protein were highly protected (described previously), as were those vaccinated with the 42-kDa protein that contained the 19-kDa fragment. The N-terminally expressed fragment of P. yoelii was not full length because of proteolytic cleavage in E. coli. The GST-82-kDa partial fragments induced some immunity, but the surviving mice still had high parasitemias. Vaccination with the peptide from the middle region of MSP1 gave minimal to no protection. Therefore, in addition to the C-terminal 19- and 42-kDa proteins, the only other fragment to give protection was the 82-kDa protein. The protection induced by the truncated 82-kDa protein was minimal compared with that of the C-terminal fragments.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
41 articles.
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