title: Induction of protective CTL responses against the Plasmodium yoelii circumsporozoite protein by immunization with peptides.
abstract: To determine the optimum combination, concentration, and formulation of synthetic peptides and adjuvants to induce protective CTL responses against the Plasmodium yoelii circumsporozoite protein (PyCSP), BALB/c mice were immunized with linear and multiple antigen peptides (MAP) including PyCSP CTL and Th epitopes in Montanide's ISA51, Lipofectin, and Lipofectamine. An H-2K(d)-restricted PyCSP CTL epitope, SYVPSAEQI (amino acids (aa) 280-288), recognized by protective CTL clones, was included in the following peptides: a 9-aa linear peptide (SYVPSAEQI; PyCSP9), a 20-aa linear peptide (aa 280-299; SYVPSAEQILEFVKQISSL; PyCSP20), a MAP containing four branches of PyCSP20 (MAP(280-299)), and a linear peptide and a MAP(MAP(280-299)p2p30) in which PyCSP20 was colinearly synthesized with two universal Th epitopes from tetanus toxin (p2p30). A MAP containing the PyCSP Th epitope (aa 57-70; KIYNRNIVNRLLGD) was included in some experiments. The highest specific lytic activity against peptide-pulsed target cells was obtained with splenocytes from mice immunized with three doses at 3-wk intervals of MAP(280-299)p2p30 in Lipofectin or Lipofectamine. Forty percent of the mice immunized with MAP(280-299)p2p30 and Lipofectin were protected against sporozoite challenge. Immunization with CTL and Th epitopes co-linearly synthesized in a MAP induced significantly better CTL than did immunization with the same sequence as a linear peptide, or immunization with a mixture of two individual MAPs, one with the CTL epitope and the second with the Th epitope.
authors.affiliation: Naval Medical Research Institute, Malaria Program, Rockville, MD 20852, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Franke
authors.forename: G
authors.initials: G
authors.lastname: Corradin
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007279:Injections, Subcutaneous; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000276:immunology; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry / Q000276:immunology; D013744:Tetanus Toxin / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D008081:Liposomes; D010446:Peptide Fragments; D010714:Phosphatidylethanolamines; D015800:Protozoan Proteins; D013744:Tetanus Toxin; C041595:circumsporozoite protein, Protozoan; C020888:1,2-dielaidoylphosphatidylethanolamine