Differential antibody responses to Plasmodium falciparum-derived B-cell epitopes induced by diepitope multiple antigen peptides (MAP) containing different T-cell epitopes

Epitopes of universal character are needed when designing subunit vaccines against infectious diseases such as malaria. We have compared the immunogenicity of B-cell epitopes from the Plasmodium falciparum antigen repeats DPNANPNV (PfCS protein) and VTEEI (Pf332) when assembled with four different universal T-cell epitopes in diepitope multiple antigen peptides (MAP). T-epitopes employed were from P. falciparum antigens (CS.T3, [T-*](4) and EBP3) or from the Clostridium tetani toxin (P2). In association with either of the T-epitopes, the genetic unresponsiveness to the B-epitopes was successfully bypassed. Our results show that the immunogenicity of a T-epitope alone does not necessarily predict the ability of the T-epitope to provide T-cell help when combined with other epitopes in an immunogen. Further, the nature of the immune responses in terms of total IgG antibodies and their subclass distribution, T-cell proliferation and IFN-gamma production, varied with the T-epitope and mouse strain, which may indicate the need for inclusion of a combination of different universal T-epitopes in a future malaria subunit vaccine. (C) 2004 Elsevier Ltd. All rights reserved.