Plasmodium berghei subunit vaccine: repeat synthetic peptide of circumsporozoite protein comprising T- and B-cell epitopes fails to confer immunity.
In the murine malaria model induced by Plasmodium berghei, we studied the immunogenicity of the repeat region of the circumsporozoite (CS) protein, which is the main target of the antibody response in infected animals. We immunized several strains with a synthetic peptide--Y(DPPPPNPN)3--corresponding to one of the two P. berghei repeat sequences in complete Freund's adjuvant. Only C57BL/6 immune sera reacted with the synthetic peptide in ELISA and with the native CS protein on P. berghei sporozoites, as detected by immunofluorescence. From lymph node cells of immunized C57BL/6 we isolated two repeat-specific T-cell lines which proliferated in the presence of the synthetic peptide or the recombinant CS protein. We analysed the protective role of this repeat-specific response by injecting infectious sporozoites into mice immunized with irradiated sporozoites or with the repeat peptide. The percentage of mice developing parasitaemia was 80-90% in the peptide-immunized group and only 10-20% in the group immunized with irradiated sporozoites. Anti-repeat antibody titres were comparable in the two groups. On the basis of these results, we can conclude that the T- and B-cell response to the CS repeat obtained with this synthetic peptide immunization is not sufficient for a protective immunity.
Migliorini
P
P
Institut of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Boulanger
N
N
Betschart
B
B
Corradin
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007109:Immunity / Q000276:immunology; D008288:Malaria / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000276:immunology; D015800:Protozoan Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D015800:Protozoan Proteins; D014612:Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan