Establishment of a New Zealand White Rabbit Model for Lethal Toxin (LT) Challenge and Efficacy of Monoclonal Antibody 5E11 in the LT-Challenged Rabbit Model

Abstract

Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11 needs proper animal models. However, anthrax spores are extremely dangerous, so experiments must be conducted under Biosafety Level 3 conditions. Considering the critical effects of lethal toxin (LT) on hosts during infection, we report the establishment of a LT-challenged rabbit model, which caused 100% mortality with a dose of 2 mg PA + 1 mg LF, while a 4 mg PA + 2 mg LF challenge could limit death to within three days. Then, we evaluated 5E11 efficacy against LT. A prophylactic study showed that the i.v. administration of 40 mg/kg 5E11 four days before lethal dose LT challenge could lead to 100% survival. In therapeutic studies, the i.v. administration of 40 mg/kg 5E11 10 min after lethal dose LT challenge could provide complete protection. Overall, we developed a new LT-challenged rabbit model, and our results indicate that 5E11 shows potential for the clinical application in anthrax treatment.

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination

“…The mice in the control group were administrated the isotype mAb 5E11. 46 The mouse weights and survival were recorded daily for 14 days post-infection. In addition, mouse lung tissues were collected at 3 days post-infection for the assessment of virus replication and histopathological changes.…”

Bacillus anthracis lethal toxin, but not edema toxin, increases pulmonary artery pressure and permeability in isolated perfused rat lungs

“…Increased permeability with LT exposure at either the alveolar endothelial or epithelial levels or both could produce direct alveolar protein and fluid accumulation, ventilation and perfusion mismatching, and hypoxia and reduced lung compliance. Histopathology studies have demonstrated alveolar protein and fluid accumulation in some but not all models (13,28,39,64). Permeability increases in the pleural visceral or parietal tissues, could also contribute to the recurrent pleural effusions that characterize inhalational anthrax disease.…”