title: Conversion of poorly immunogenic malaria repeat sequences into a highly immunogenic vaccine candidate.
abstract: The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. In order to optimize immunogenicity, well-characterized CSP-specific neutralizing B cell epitopes and a universal T cell epitope were combined with an efficient and flexible particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. The vaccine candidate, V12.PF3.1, is a potent immunogen in mice eliciting unprecedented levels (greater than 10(6) titers) of sporozoite-binding antibodies after only two doses. The anti-sporozoite antibodies are long lasting, represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. These and other characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.
authors.affiliation: Vaccine Research Institute of San Diego (VRISD), 3030 Science Park Road, Suite 100, San Diego, CA 92121, USA. dmilich@vrisd.org
authors.forename: D R
authors.initials: DR
authors.lastname: Milich
authors.forename: J
authors.initials: J
authors.lastname: Hughes
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Sällberg
authors.forename: T R
authors.initials: TR
authors.lastname: Phillips
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics; D007700:Kinetics; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan