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
- 1 July 1990
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 20 (7), 1619-1622
- https://doi.org/10.1002/eji.1830200733
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.Keywords
This publication has 22 references indexed in Scilit:
- Immune responses to defined epitopes of the circumsporozoite protein of the murine malaria parasite, Plasmodium yoeliiEuropean Journal of Immunology, 1990
- Plasmodium berghei Subunit Vaccine: Repeat Synthetic Peptide of Circumsporozoite Protein Comprising T- and B-Cell Epitopes Fails to Confer ImmunityScandinavian Journal of Immunology, 1990
- Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cellsEuropean Journal of Immunology, 1989
- 1H‐nmr studies of synthetic polypeptide models of Plasmodium falciparum circumsporozoite protein tandemly repeated sequenceBiopolymers, 1989
- A malaria T-cell epitope recognized in association with most mouse and human MHC class II moleculesNature, 1988
- Genetic restriction of the murine humoral response to a recombinant Plasmodium vivax circumsporozoite proteinEuropean Journal of Immunology, 1988
- Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoitesNature, 1987
- Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine.The Journal of Experimental Medicine, 1986
- Neutralization of the infectivity of sporozoites of Plasmodium knowlesi by antibodies to a synthetic peptide.The Journal of Experimental Medicine, 1984
- Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection.The Journal of Experimental Medicine, 1980