title: A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge.
abstract: We have developed a therapeutic for the treatment of anthrax using an affinity-enhanced monoclonal antibody (ETI-204) to protective antigen (PA), which is the central cell-binding component of the anthrax exotoxins. ETI-204 administered preexposure by a single intravenous injection of a dose of between 2.5 and 10 mg per animal significantly protected rabbits from a lethal aerosolized anthrax spore challenge ( approximately 60 to 450 times the 50% lethal dose of Bacillus anthracis Ames). Against a similar challenge, ETI-204 administered intramuscularly at a 20-mg dose per animal completely protected rabbits from death (100% survival). In the postexposure setting, intravenous administration of ETI-204 provided protection 24 h (8 of 10) and 36 h (5 of 10) after spore challenge. Administration at 48 h postchallenge, when 3 of 10 animals had already succumbed to anthrax infection, resulted in the survival of 3 of 7 animals (43%) for the duration of the study (28 days). Importantly, surviving ETI-204-treated animals were free of bacteremia by day 10 and remained so until the end of the studies. Only 11 of 51 ETI-204-treated rabbits had positive lung cultures at the end of the studies. Also, rabbits that were protected from inhalational anthrax by administration of ETI-204 developed significant titers of PA-specific antibodies. Presently, the sole therapeutic regimen available to treat infection by inhalation of B. anthracis spores is a 60-day course of antibiotics that is effective only if administered prior to or shortly after exposure. Based upon results reported here, ETI-204 is an effective therapy for prevention and treatment of inhalational anthrax.
authors.affiliation: Elusys Therapeutics Inc., P.O. Box 102, 25 Riverside Drive, Pine Brook, NJ 07058, USA.
authors.forename: Nehal
authors.initials: N
authors.lastname: Mohamed
authors.forename: Michelle
authors.initials: M
authors.lastname: Clagett
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Steven
authors.initials: S
authors.lastname: Jones
authors.forename: Steven
authors.initials: S
authors.lastname: Pincus
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Alia
authors.forename: Linda
authors.initials: L
authors.lastname: Nardone
authors.forename: Michael
authors.initials: M
authors.lastname: Babin
authors.forename: George
authors.initials: G
authors.lastname: Spitalny
authors.forename: Leslie
authors.initials: L
authors.lastname: Casey
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control* / Q000662:veterinary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D000942:Antigens, Bacterial / Q000276:immunology*; D000992:Antitoxins; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D001769:Blood / Q000382:microbiology; D007273:Injections, Intramuscular; D011817:Rabbits; D013171:Spores, Bacterial; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; C030325:anthrax toxin; C000611266:obiltoxaximab