INDUCTION OF CYTOLYTIC AND ANTIBODY-RESPONSES USING PLASMODIUM-FALCIPARUM REPEATLESS CIRCUMSPOROZOITE PROTEIN ENCAPSULATED IN LIPOSOMES

Plasmodium circumsporozoite (CS) protein-induced antibody and T-cell r esponses are considered to be important in protective immunity. Since the key repeat determinant of the CS protein may actually restrict the recognition of other potential T- and B-cell sites, a modified Plasmo dium falciparum CS protein lacking the central repeat region, RLF, was expressed in Escherichia coli. On purification, RLF was encapsulated into liposomes [L(RLF)] and used for the in vivo induction of cytolyti c T lymphocytes (CTL) and antibodies. Immunization of B10.Br (H-2k) mi ce with L(RLF), but not with RLF, induced CD8+ CTL specific for the P. falciparum CS protein CTL epitope, amino acid residues 368-390. Anti- L(RLF) serum reacted with antigens on intact sporozoites and inhibited sporozoite invasion of hepatoma cells. Antibody specificity studies i n New Zealand White rabbits revealed new B-cell sites localized in ami no acid residues 84-94, 91-99, 97-106 and 367-375. Although the mechan isms by which liposomes enhance cellular and humoral immune responses remain unknown, liposome-formulated vaccines have been well tolerated in humans; hence, their use in vaccines, when efficacy depends on anti body and CTL responses, may be broadly applicable.