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A multiple antigen peptide from the repetitive sequence of the Plasmodium malariae circumsporozoite protein induces a specific antibody response in mice of various H‐2 haplotypes

A multiple antigen peptide from the repetitive sequence of the Plasmodium malariae... The major repetitive epitopes of the surface circumsporozoite (CS) protein of malaria sporozoites represent candidates for the development of subunit vaccines against malaria. However, previous experimental work has shown that repetitive peptides from the CS proteins of Plasmodium falciparum, P. vivax, P. yoelii and P. berghei are immunogenic only in mice with the H‐2b or H‐2k haplotype. This led to the conclusion that strong T helper epitopes from the non‐repetitive CS sequences were required in the design of sporozoite vaccines. In the present study, we investigated the immunogenicity in mice of a octa‐branched multiple antigen peptide (MAP) containing repeats of the CS protein of the human malaria parasite, P. malariae, (MAP8(NAAG)6), and found that mice with an H‐2b, H‐2d, H‐2k, H‐2f, H‐2q, and H‐2s haplotype produced anti‐peptide antibodies after immunization and that only H‐2r mice were nonresponsive. This antibody response, not induced in athymic H‐2b nulnu mice, was directed against the (NAAG) sequence, but not against the lysine core of the MAP construct. Finally, when covalently linked to a synthetic polymer of the repetitive (NANP) sequence of the P. falciparum CS protein, (MAPs(NAAG)6) behaved as a carrier molecule for the production of anti‐(NANP)n antibodies in H‐2d and H‐2k mice, genetically nonresponder to the (NANP)n sequence. Should this wide immunogenicity of the P. malariae CS (NAAG) repetitive sequence also apply to humans, it might be considered for the design of multivalent subunit malaria vaccines. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Immunology Wiley

A multiple antigen peptide from the repetitive sequence of the Plasmodium malariae circumsporozoite protein induces a specific antibody response in mice of various H‐2 haplotypes

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References (24)

Publisher
Wiley
Copyright
Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
0014-2980
eISSN
1521-4141
DOI
10.1002/eji.1830200733
pmid
2201549
Publisher site
See Article on Publisher Site

Abstract

The major repetitive epitopes of the surface circumsporozoite (CS) protein of malaria sporozoites represent candidates for the development of subunit vaccines against malaria. However, previous experimental work has shown that repetitive peptides from the CS proteins of Plasmodium falciparum, P. vivax, P. yoelii and P. berghei are immunogenic only in mice with the H‐2b or H‐2k haplotype. This led to the conclusion that strong T helper epitopes from the non‐repetitive CS sequences were required in the design of sporozoite vaccines. In the present study, we investigated the immunogenicity in mice of a octa‐branched multiple antigen peptide (MAP) containing repeats of the CS protein of the human malaria parasite, P. malariae, (MAP8(NAAG)6), and found that mice with an H‐2b, H‐2d, H‐2k, H‐2f, H‐2q, and H‐2s haplotype produced anti‐peptide antibodies after immunization and that only H‐2r mice were nonresponsive. This antibody response, not induced in athymic H‐2b nulnu mice, was directed against the (NAAG) sequence, but not against the lysine core of the MAP construct. Finally, when covalently linked to a synthetic polymer of the repetitive (NANP) sequence of the P. falciparum CS protein, (MAPs(NAAG)6) behaved as a carrier molecule for the production of anti‐(NANP)n antibodies in H‐2d and H‐2k mice, genetically nonresponder to the (NANP)n sequence. Should this wide immunogenicity of the P. malariae CS (NAAG) repetitive sequence also apply to humans, it might be considered for the design of multivalent subunit malaria vaccines.

Journal

European Journal of ImmunologyWiley

Published: Jul 1, 1990

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