Human monoclonal anti-protective antigen antibody for the low-dose post-exposure prophylaxis and treatment of Anthrax

Qi Tang,Yiwen Wang,Changjun Wang,Zhenqing Feng,Jin Zhu,Xudong Liang,Xingwang Kuai,Siping Xiong

doi:10.1186/s12879-018-3542-6

Abstract

BackgroundDisease caused by Bacillus anthracis is often accompanied by high mortality primarily due to toxin-mediated injury. In the early disease course, anthrax toxins are secreted; thus, antibiotic use is limited to the early stage. In this regard, antibodies against the toxin component, protective antigen (PA), play an important role in protecting against anthrax. Therefore, we developed PA21, a fully human anti-PA immunoglobulin G monoclonal antibody.MethodsCombining human Fab was screened from a phage library with human heavy constant regions. Enzyme-linked immune sorbent assay, Western blot analysis and immunoprecipitation test evaluated the binding ability of PA21. Moreover, the affinity and neutralizing activity of the antibody was detected in vitro while the protective effectiveness in 60 rats was also examined in vivo.ResultsThe Fischer 344 rats challenged with the lethal toxin can be protected by PA21 at a concentration of 0.067 mg/kg. All six rats remained alive although PA21 was injected 24 h before the toxin challenge. PA21 did not influence the binding of PA to cell receptors and that of a lethal factor to PA.ConclusionThe PA21 monoclonal antibody against PA can be used for emergency prophylaxis and anthrax treatment.

Highlights

Disease caused by Bacillus anthracis is often accompanied by high mortality primarily due to toxinmediated injury
The anthrax toxin is composed of a protective antigen (PA), a lethal factor (LF) and an edema factor (EF)
Through immunoprecipitation, a protein of approximately 83 kDa in size was detected by Sodium dodecyl sulphate (SDS)–Polyacrylamide gel electrophoresis (PAGE); the band was analyzed by mass spectra, compared with the Swiss-Prot database and analyzed for B. anthracis PA (Fig.3a and b)

Summary

Introduction

Disease caused by Bacillus anthracis is often accompanied by high mortality primarily due to toxinmediated injury. In the early disease course, anthrax toxins are secreted; antibiotic use is limited to the early stage. In this regard, antibodies against the toxin component, protective antigen (PA), play an important role in protecting against anthrax. The anthrax toxin, which is a mixture of three secreted proteins, plays a crucial role in the death of humans and animals affected by anthrax [3]. The anthrax toxin is composed of a protective antigen (PA), a lethal factor (LF) and an edema factor (EF). These three proteins are individually nontoxic, but PA combines with LF and EF can form the lethal toxin (LT) and edema toxin (ET), respectively [4, 5]. LF causes cell death and EF causes cell edema [14, 15]

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Conclusion