title: Presentation of peptides from Bacillus anthracis protective antigen on Tobacco Mosaic Virus as an epitope targeted anthrax vaccine.
abstract: The current anthrax vaccine requires improvements for rapidly invoking longer-lasting neutralizing antibody responses with fewer doses from a well-defined formulation. Designing antigens that target neutralizing antibody epitopes of anthrax protective antigen, a component of anthrax toxin, may offer a solution for achieving a vaccine that can induce strong and long lasting antibody responses with fewer boosters. Here we report implementation of a strategy for developing epitope focused virus nanoparticle vaccines against anthrax by using immunogenic virus particles to present peptides derived from anthrax toxin previously identified in (1) neutralizing antibody epitope mapping studies, (2) toxin crystal structure analyses to identify functional regions, and (3) toxin mutational analyses. We successfully expressed two of three peptide epitopes from anthrax toxin that, in previous reports, bound antibodies that were partially neutralizing against toxin activity, discovered cross-reactivity between vaccine constructs and toxin specific antibodies raised in goats against native toxin and showed that antibodies induced by our vaccine constructs also cross-react with native toxin. While protection against intoxication in cellular and animal studies were not as effective as in previous studies, partial toxin neutralization was observed in animals, demonstrating the feasibility of using plant-virus nanoparticles as a platform for epitope defined anthrax vaccines.
authors.affiliation: Keck Graduate Institute, Claremont, CA, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: McComb
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Chi-Lee
authors.initials: CL
authors.lastname: Ho
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Bradley
authors.affiliation: Keck Graduate Institute, Claremont, CA, USA. Electronic address: Larry_Grill@kgi.edu.
authors.forename: Laurence K
authors.initials: LK
authors.lastname: Grill
authors.affiliation: Keck Graduate Institute, Claremont, CA, USA. Electronic address: Mikhail_Martchenko@kgi.edu.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Martchenko
mesh_terms: D000818:Animals; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D004337:Drug Carriers; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D006041:Goats; D008810:Mice, Inbred C57BL; D014027:Tobacco Mosaic Virus / Q000235:genetics*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004337:Drug Carriers; D000939:Epitopes; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C030325:anthrax toxin
keywords: Anthrax; Bacillus anthracis; Epitope focused vaccine; Protective antigen; Tobacco Mosaic Virus; Virus nanoparticle vaccine