Fine specificity of immune responses to epitopic sequences in synthetic peptides containing B and T epitopes from the conserved Plasmodium falciparum blood-stage antigens

Abstract

Immunisation with two chemically synthesised, linear, multiple epitope peptides (MEP) containing B and T cell epitopes from two conserved blood-stage antigens of the human malaria parasite, Plasmodium falciparum, induced high levels of circulating antibodies without the use of a carrier protein. Immunisation of BALB/c mice with MEP constructs (P1 and P2) induced antibodies against the various epitope sequences included in their structures, although the immune response was focused more towards the N terminal and the middle portion of the peptides. In vitro T cell proliferation assays indicated that only one of the two Th epitopes included in P1 and P2 are functional. Both P1 and P2, based on P. falciparum sequences, cross-reacted with sera from P. yoelii-infected mice. Immunisation with P1 in CFA, but not with P2, provided partial protection to BALB/c mice against P. yoelii challenge infection. Peptide P1 was highly immunogenic in alum also, and a somewhat higher level of protection was observed as compared to CFA immunisation. We found that immunisation with P1 induced antibody responses in different strains of mice, although to different extents. These results suggest that linear, multiple epitope peptides may offer attractive alternatives as subunit vaccine candidate molecules, but at the same time highlight the fact that the design principles are far from being clear and have yet to be worked out.