IN HUMAN MALARIA PROTECTIVE ANTIBODIES ARE DIRECTED MAINLY AGAINST THE LYS-GLU ION-PAIR WITHIN THE LYS-GLU-LYS MOTIF OF THE SYNTHETIC VACCINE SPF-66

The KEK (Lysine-Glutamic acid-Lysine) motif is frequently found in the primary structure of certain malaria proteins involved in invasion, and plays an important role in the interaction of these proteins with the erythrocyte. This motif is contained in a peptide which forms part of the polymeric synthetic malaria vaccine SPf 66, currently undergoing extensive human trials. Analysis of the antibody titres against the subunit peptides that comprise this vaccine has shown that protection is associated with high titres to the KEK-containing peptide. In this paper we examine the fine recognition of this motif by polyclonal sera from protected vaccinated individuals, demonstrating the critical role played by the interacting ion pair formed between the amino terminal lysine (K) and glutamic acid (E), which act as contact residues for an important proportion of the antibody population directed against this vaccine. This ion pair in the KEK motif constitutes perhaps one of the most important malaria epitopes involved in protection, and could explain the mechanism through which protective immunity is acquired.