Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein.
The circumsporozoite (CS) protein of Plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell site was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high-titer antibody response was formed. This peptide sequence could prime helper T cells for a secondary response to the intact CS protein. The new helper T-cell site is located outside the repetitive region of the CS protein and appears to be the immunodominant T site on the molecule. This approach should be useful in the rational design and construction of vaccines.
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D051379:Mice; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D014612:Vaccines; C041595:circumsporozoite protein, Protozoan