Construction of synthetic immunogens: use of T- and B-cell epitopes of CS and RESA proteins of Plasmodium falciparum.
An invariant T-helper epitope of the sequence ENDIEKKICKMEKCSSVFNV (residue no. 376-395) from the circumsporozoite (CS) protein was coupled chemically with the repeat sequences, namely (EENV)2, EENVEHDA and DDEHVEEPTVA, of ring-infected erythrocyte surface antigen (RESA) protein of Plasmodium falciparum. The CS sequence was tested for helper and proliferative activity in five inbred strains of mice of different haplotypes. The CS peptide showed dose-dependent lymphocyte proliferative response in all the strains tested. On the other hand, no proliferative response was observed with the dimers of the three RESA repeat sequences. The antibody levels in these strains immunized with RESA-CS hybrid structures showed high titres and a booster effect during subsequent immunization. Such a phenomenon was not observed with RESA peptides alone. The above CS sequence could be an ideal T-helper epitope which can be linked to hydrophilic B-cell epitopes of the RESA sequence to overcome major histocompatibility complex restriction in the host.
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000187:drug effects; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D000954:Antigens, Surface / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology*; D015202:Protein Engineering; D015800:Protozoan Proteins; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D010446:Peptide Fragments; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum