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 tetrapepti de tuftsin (TKPR), was chemically linked to EENVEHDA and DDEHVEEPTVA r epeat sequences of ring-infected erythrocyte surface antigen protein ( an asexual blood-stage antigen) of Plasmodium falciparum. These synthe tic constructs were tested for their humoral and cellular immune respo nses in five inbred strains of mice with different genetic backgrounds (H-2(a), H-2(b), H-2(d), H-2(k) and H-2(i)). Mice immunized with thes e constructs showed higher antibody titres, secondary immune responses and antigen-induced T-cell proliferation compared with the peptide di mers alone. Sera from mice immunized with both the constructs inhibite d merozoite invasion of erythrocytes in vitro by 60-80% at 1:10 antise ra dilution. Polytuftsin alone proved to be a very poor immunogen in o ur studies, since no anti-tuftsin antibodies could be detected in the sera. Therefore, we conclude that the synthetic constructs described h ere could be useful for the development of subunit malaria vaccines.