A High-Affinity Monoclonal Antibody to Anthrax Protective Antigen Passively Protects Rabbits before and after Aerosolized Bacillus anthracis Spore Challenge

N Mohamed, M Clagett, J Li, S Jones… - Infection and …, 2005 - Am Soc Microbiol
N Mohamed, M Clagett, J Li, S Jones, S Pincus, G D'alia, L Nardone, M Babin, G Spitalny…
Infection and immunity, 2005Am Soc Microbiol
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 (∼ 60 to 450 times the 50% lethal
dose of Bacillus anthracis Ames). Against a similar challenge, ETI-204 administered …
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 (∼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.
American Society for Microbiology