title: Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection.
abstract: An intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. Protective antigen (PA)-based vaccines are most favored as immune responses directed against PA are singularly protective, although the actual protective mechanism remains to be unraveled. Herein we show that contrary to the prevailing view, an efficacious PA-based vaccine confers protection against inhalation anthrax by preventing the establishment of a toxin-releasing systemic infection. Equally importantly, antibodies measured by the in vitro lethal toxin neutralization activity assay (TNA) that is considered as a reliable correlate of protection, especially for PA protein-based vaccines adjuvanted with aluminum salts appear to be not absolutely essential for this protective immune response.
authors.affiliation: Center for Biologics Evaluation and Research; Food and Drug Administration; Bethesda, MD USA.
authors.forename: Tod J
authors.initials: TJ
authors.lastname: Merkel
authors.forename: Pin-Yu
authors.initials: PY
authors.lastname: Perera
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Lee
authors.forename: Anita
authors.initials: A
authors.lastname: Verma
authors.forename: Toyoko
authors.initials: T
authors.lastname: Hiroi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokote
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Liyanage P
authors.initials: LP
authors.lastname: Perera
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D005260:Female; D006801:Humans; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin
keywords: IL-15; anthrax; bioluminescence; protective antigen; vaccines; vaccinia