title: Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys.
abstract: Bacillus anthracis, the causative agent of anthrax, is recognized as one of the most serious bioterrorism threats. The current human vaccines are based on the protective antigen component of the anthrax toxins. Concern about possible vaccine resistant strains and reliance on a single antigen has prompted the search for additional immunogens. Bacterial capsules, as surface-expressed virulence factors, are well-established components of several licensed vaccines. In a previous study we showed that an anthrax vaccine consisting of the B. anthracis poly-γ-D-glutamic acid capsule covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B protected mice against parenteral B. anthracis challenge. Here we tested this vaccine in rabbits and monkeys against an aerosol spore challenge. The vaccine induced anti-capsule antibody responses in both species, measured by ELISA and a macrophage opsono-adherence assay. While rabbits were not protected against a high aerosol challenge dose, significant protection was observed in monkeys receiving the capsule conjugate vaccine. The results confirm that the capsule is a protective immunogen against anthrax, being the first non-toxin antigen shown to be efficacious in monkeys and suggest that addition of capsule may broaden and enhance the protection afforded by protective antigen-based vaccines.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Chabot
authors.forename: Joseph
authors.initials: J
authors.lastname: Joyce
authors.forename: Michael
authors.initials: M
authors.lastname: Caulfield
authors.forename: James
authors.initials: J
authors.lastname: Cook
authors.forename: Robert
authors.initials: R
authors.lastname: Hepler
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vietri
authors.forename: Gordon
authors.initials: G
authors.lastname: Ruthel
authors.forename: Wesley
authors.initials: W
authors.lastname: Shoop
authors.forename: Louise
authors.initials: L
authors.lastname: Pitt
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Leffel
authors.forename: Wilson
authors.initials: W
authors.lastname: Ribot
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Friedlander
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D016667:Bacterial Capsules / Q000737:chemistry / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000302:isolation & purification; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology; D008297:Male; D009345:Neisseria meningitidis / Q000737:chemistry; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis; D011817:Rabbits; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D009895:Opsonin Proteins; D018074:Vaccines, Conjugate