Construction of a synthetic immunogen: use of the natural immunomodulator polytuftsin in malaria vaccines against RESA antigen of Plasmodium falciparum.

Polytuftsin, a 35-40-unit repeat of the naturally occurring tetrapeptide tuftsin (TKPR), was chemically linked to EENVEHDA and DDEHVEEPTVA repeat sequences of ring-infected erythrocyte surface antigen protein (an asexual blood-stage antigen) of Plasmodium falciparum. These synthetic constructs were tested for their humoral and cellular immune responses in five inbred strains of mice with different genetic backgrounds (H-2a, H-2b, H-2d, H-2k and H-2i). Mice immunized with these constructs showed higher antibody titres, secondary immune responses and antigen-induced T-cell proliferation compared with the peptide dimers alone. Sera from mice immunized with both the constructs inhibited merozoite invasion of erythrocytes in vitro by 60-80% at 1:10 antisera dilution. Polytuftsin alone proved to be a very poor immunogen in our studies, since no anti-tuftsin antibodies could be detected in the sera. Therefore, we conclude that the synthetic constructs described here could be useful for the development of subunit malaria vaccines.