Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine

Compared with a single-stage antigen-based vaccine, a multistage and multiv alent Plasmodium falciparum vaccine would be more efficacious by inducing " multiple layers" of immunity, We have constructed a synthetic gene that enc odes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte ep itopes derived from 9 stage-specific P. falciparum antigens corresponding t o the sporozoite, liver, erythrocytic asexual, and sexual stages, The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/N IIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that r ecognized vaccine antigen, linear peptides contained in the vaccine, and al l stages of P, falciparum. In vitro assays of protection revealed that the vaccine elicited antibodies strongly inhibited sporozoite invasion of hepat oma cells and growth of blood-stage parasites in the presence of monocytes, These observations demonstrate that a multicomponent, multistage malaria v accine can induce immune responses that inhibit parasite development at mul tiple stages. The rationale and approach used in the development of a multi component P, falciparum vaccine will be useful in the development of a mult ispecies human malaria vaccine and vaccines against other infectious diseas es.