title: A malaria vaccine candidate based on a hepatitis B virus core platform.
abstract: OBJECTIVE
  The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes.
  
  
  METHODS
  Well-characterized CSP-specific neutralizing B cell epitopes and a 'universal' T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate.
  
  
  RESULTS
  The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 106 titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and 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.
  
  
  CONCLUSIONS
  These 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: Division of Clinical Virology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Sällberg
authors.forename: Janice
authors.initials: J
authors.lastname: Hughes
authors.forename: Joyce
authors.initials: J
authors.lastname: Jones
authors.forename: Tom R
authors.initials: TR
authors.lastname: Phillips
authors.forename: David R
authors.initials: DR
authors.lastname: Milich
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D007114:Immunization; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D020449:Repetitive Sequences, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan