The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Bacillus anthracis Infection in BALB/c Mice and...

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Inhalational anthrax, caused by Bacillus anthracis, poses a significant bioterrorism threat.
• Effective countermeasures are crucial for public health preparedness.
• The development of novel antibiotics like TP-271 is essential to combat anthrax.

Purpose of the Study:

• To evaluate the efficacy of the fluorocycline TP-271 as a postexposure prophylaxis and treatment for inhalational anthrax.
• To assess TP-271's effectiveness in both murine and nonhuman primate models.

Main Methods:

• BALB/c mice were exposed to Bacillus anthracis Ames spores and treated with TP-271 at various doses and time points post-challenge.
• Cynomolgus macaques were infected with B. anthracis spores and treated with TP-271, with survival and immune responses monitored.
• Studies included postexposure prophylaxis (PEP) and treatment (Tx) arms in mice, and a 14- or 21-day treatment regimen in nonhuman primates.

Main Results:

• In mice, TP-271 treatment resulted in high survival rates (84-95% for PEP, 81-100% for Tx) across different doses and initiation times.
• In nonhuman primates, 21-day TP-271 treatment led to 100% survival, while 14-day treatment resulted in 67% survival, compared to 0% in controls.
• Survivors in both models developed toxin-neutralizing and anti-protective antigen IgG antibodies, indicating a robust immune response.

Conclusions:

• TP-271 exhibits significant therapeutic potential against inhalational anthrax in preclinical models.
• The drug demonstrated efficacy when administered both prophylactically and therapeutically.
• TP-271 represents a promising candidate for a new inhalational anthrax countermeasure.