title: Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms.
abstract: A new anthrax vaccine under clinical investigation is based on recombinant Bacillus anthracis protective antigen (rPA). Here, we investigated microneedle-based cutaneous and nasal mucosal delivery of rPA in mice and rabbits. In mice, intradermal (id) delivery achieved up to 90% seroconversion after a single dose, compared with 20% after intramuscular (im) injection. Intranasal (inl) delivery of a liquid formulation required 3 doses to achieve responses that were comparable with those achieved via the id or im routes. In rabbits, id delivery provided complete protection against aerosol challenge with anthrax spores; in addition, novel powder formulations administered inl provided complete protection, whereas a liquid formulation provided only partial protection. These results demonstrate, for the first time, that cutaneous or nasal mucosal administration of rPA provides complete protection against inhalational anthrax in rabbits. The novel vaccine/device combinations described here have the potential to improve the efficacy of rPA and other biodefense vaccines.
authors.affiliation: BD Technologies, 21 Davis Dr., Research Triangle Park, NC 27709, USA. john_mikszta@bd.com
authors.forename: John A
authors.initials: JA
authors.lastname: Mikszta
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Sullivan
authors.forename: Cheryl
authors.initials: C
authors.lastname: Dean
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Waterston
authors.forename: Jason B
authors.initials: JB
authors.lastname: Alarcon
authors.forename: John P
authors.initials: JP
authors.lastname: Dekker
authors.forename: John M
authors.initials: JM
authors.lastname: Brittingham
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: C Robin
authors.initials: CR
authors.lastname: Hwang
authors.forename: Matthew
authors.initials: M
authors.lastname: Ferriter
authors.forename: Ge
authors.initials: G
authors.lastname: Jiang
authors.forename: Kevin
authors.initials: K
authors.lastname: Mar
authors.forename: Kamal U
authors.initials: KU
authors.lastname: Saikh
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Stiles
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Noel G
authors.initials: NG
authors.lastname: Harvey
mesh_terms: D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D016503:Drug Delivery Systems; D051379:Mice; D011817:Rabbits; D014611:Vaccination
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial