Development of protective immunity in New Zealand White rabbits challenged with Bacillus anthracis spores and treated with antibiotics and obiltoxaximab, a monoclonal antibody against protective antigen [PublishAheadOfPrint]

Recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax Protective Antigen (PA) is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for treatment of inhalational anthrax. Because of spore latency, disease re-emergence after treatment cessation is a concern and there is a need to understand development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in NZW rabbits challenged with a targeted lethal dose of B. anthracis spores and treated with antibiotics, obiltoxaximab or a combination of both. Survivors of the primary challenge were re-challenged 9 month later, and monitored for survival. Survival rates after primary and re-challenge, for controls and animals treated with obiltoxaximab, levofloxacin or a combination of both were 0, 65, 100, 95% and 0, 100, 95, 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin neutralizing titers prior to re-challenge. Following re-challenge, systemic bacteremia and toxemia were not detected in most animals and levels of circulating anti-PA IgG titers increased starting 5 days post re-challenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves survival of rabbits that received a lethal inhalation B. anthracis spore challenge and does not interfere with development of immunity. Survivors of primary challenge are protected against re-exposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response.

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