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

Toxins
Duanyang ZhangWei Chen

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.

References

Sep 9, 1999·The New England Journal of Medicine·T C DixonP C Hanna
Jun 19, 2004·The Journal of Antimicrobial Chemotherapy·A AthamnaE Rubinstein
May 13, 2006·Molecular Microbiology·Thomas Candela, Agnès Fouet
Jun 30, 2009·Molecular Aspects of Medicine·Jean-Nicolas TournierCosima T Baldari
Jul 10, 2009·The New England Journal of Medicine·Thi-Sau MigoneSally D Bolmer
Jul 30, 2009·Molecular Aspects of Medicine·Mahtab Moayeri, Stephen H Leppla
Oct 6, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hui FangDavid M Frucht
Jan 26, 2011·Antimicrobial Agents and Chemotherapy·Shay WeissZeev Altboum
Nov 10, 2011·Toxins·Tao XieDavid M Frucht
Nov 10, 2011·Toxins·Zhaochun ChenRobert Purcell
May 10, 2013·Clinical and Vaccine Immunology : CVI·Boris IoninMario H Skiadopoulos
Aug 28, 2013·Antimicrobial Agents and Chemotherapy·Nutan MytleMario H Skiadopoulos
Apr 16, 2014·Antimicrobial Agents and Chemotherapy·Nina V MalkevichMario H Skiadopoulos
Jul 22, 2015·Annual Review of Microbiology·Mahtab MoayeriShihui Liu
Dec 23, 2015·Health Security·Eileen HuangDana Meaney-Delman
Jul 20, 2016·Antimicrobial Agents and Chemotherapy·Brent J YamamotoNatalya V Serbina
Nov 5, 2016·BMC Infectious Diseases·Breanne M HeadAdrienne F A Meyers

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Citations

Feb 16, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Xizhong CuiPeter Q Eichacker

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Methods Mentioned

BETA
ELISA
electrophoresis
enzyme-linked immunosorbent assay

Software Mentioned

Phoenix WinNonlin

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