title: Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.
abstract: Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg.
authors.affiliation: Lovelace Biomedical and Environmental Research Institute (LBERI), Preclinical Drug Development, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico, United States of America.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Reed
authors.affiliation: Lovelace Biomedical and Environmental Research Institute (LBERI), Preclinical Drug Development, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico, United States of America.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Wilder
authors.affiliation: Lovelace Biomedical and Environmental Research Institute (LBERI), Preclinical Drug Development, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Mega
authors.affiliation: Lovelace Biomedical and Environmental Research Institute (LBERI), Preclinical Drug Development, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico, United States of America.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hutt
authors.affiliation: Lovelace Biomedical and Environmental Research Institute (LBERI), Preclinical Drug Development, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico, United States of America.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kuehl
authors.affiliation: Lovelace Biomedical and Environmental Research Institute (LBERI), Preclinical Drug Development, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico, United States of America.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Valderas
authors.affiliation: Pfenex Inc., 10790 Roselle St., San Diego, California, United States of America.
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Chew
authors.affiliation: Pfenex Inc., 10790 Roselle St., San Diego, California, United States of America.
authors.forename: Bertrand C
authors.initials: BC
authors.lastname: Liang
authors.affiliation: Pfenex Inc., 10790 Roselle St., San Diego, California, United States of America.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Squires
mesh_terms: D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D000881:Anthrax / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001408:Bacillus anthracis / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D011551:Pseudomonas fluorescens / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D013171:Spores, Bacterial / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C493276:Biothrax; D011994:Recombinant Proteins; C030325:anthrax toxin; D000536:Aluminum Hydroxide