Immunogenicity of synthetic peptides containing multiple epitopes from malaria antigens

Two, linear peptides, P60 and P65, have been synthesised. Both are based on region II of the circumsporozoite protein of Plasmodium falciparum (7G8), and incorporate various B- and T-cell determinants. Both were highly immunogenic in Balb/c mice even without the use of a carrier protein. However, whereas Balb/c mice immunized with P60 were partially protected against a challenge with the blood stages of a normally lethal strain of P. yoelli, similar mice immunized with P65, an analogue of P60 containing five more amino acids at the C-terminus, were completely unprotected. There were no significant differences between the cellular responses induced by each peptide in an ex-vivo, lymphocyte-proliferation assay. Although the anti-P60 antibody response was primarily directed against the N-terminal region of the peptide, the response against P65 was predominantly against the C-terminal, with very little response against the N-terminal fragments. The immunodominant B-epitopes in P60 may therefore differ from those in P65, leading to the remarkably different responses to challenge after immunization. It appears that the primary structure of epitopic peptides may affect the focus of the humoral response against the epitopes included in the peptides.