title: Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine.
abstract: Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed a synthetic gene that encodes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte epitopes derived from 9 stage-specific P. falciparum antigens corresponding to the sporozoite, liver, erythrocytic asexual, and sexual stages. The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/NIIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that recognized vaccine antigen, linear peptides contained in the vaccine, and all stages of P. falciparum. In vitro assays of protection revealed that the vaccine-elicited antibodies strongly inhibited sporozoite invasion of hepatoma cells and growth of blood-stage parasites in the presence of monocytes. These observations demonstrate that a multicomponent, multistage malaria vaccine can induce immune responses that inhibit parasite development at multiple stages. The rationale and approach used in the development of a multicomponent P. falciparum vaccine will be useful in the development of a multispecies human malaria vaccine and vaccines against other infectious diseases.
authors.affiliation: Division of Parasitic Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Y P
authors.initials: YP
authors.lastname: Shi
authors.forename: S E
authors.initials: SE
authors.lastname: Hasnain
authors.forename: J B
authors.initials: JB
authors.lastname: Sacci
authors.forename: B P
authors.initials: BP
authors.lastname: Holloway
authors.forename: H
authors.initials: H
authors.lastname: Fujioka
authors.forename: N
authors.initials: N
authors.lastname: Kumar
authors.forename: R
authors.initials: R
authors.lastname: Wohlhueter
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: W E
authors.initials: WE
authors.lastname: Collins
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D005813:Genes, Synthetic; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology* / Q000648:ultrastructure; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*