A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge.
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.
Mohamed
Nehal
N
Elusys Therapeutics Inc., P.O. Box 102, 25 Riverside Drive, Pine Brook, NJ 07058, USA.
Clagett
Michelle
M
Li
Juan
J
Jones
Steven
S
Pincus
Steven
S
D'Alia
Giovanni
G
Nardone
Linda
L
Babin
Michael
M
Spitalny
George
G
Casey
Leslie
L
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
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; C030325:anthrax toxin; C000611266:obiltoxaximab