Different mechanisms of two anti-anthrax protective antigen antibodies and function comparison between them

Siping Xiong1,2,3, Tingting Zhou1, Feng Zheng1

  • 1Epidemiological Department, Huadong Medical Institute of Biotechniques, Nanjing, 210002, China.

BMC Infectious Diseases
|November 9, 2019
PubMed
Abstract

Insights

Two anthrax antibodies, hmPA6 and PA21, were studied for their effectiveness against Bacillus anthracis toxin. PA21 demonstrated superior protection in cells and rats, while hmPA6 showed higher affinity, offering potential for combination anthrax treatment.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Bacillus anthracis toxin causes lethal disease.
  • Antibiotics are ineffective against anthrax toxin.
  • Novel antibody therapies are crucial for anthrax treatment.

Purpose of the Study:

  • Compare the efficacy and mechanisms of two anti-anthrax protective antigen (PA) antibodies, hmPA6 and PA21.
  • Elucidate the epitope recognition and neutralization strategies of these antibodies.
  • Assess their potential for anthrax treatment and prophylaxis.

Main Methods:

  • Electrophoresis, competitive ELISA, Western blot, and immunoprecipitation assays.
  • In vitro and in vivo (F344 rats) treatment studies.
  • Epitope mapping using PA domains.

Main Results:

  • PA21 exhibited superior protection in cellular and rat models compared to hmPA6.
  • hmPA6 demonstrated higher binding affinity for protective antigen (PA).
  • hmPA6 targets PA domain IV, blocking PA-receptor binding; PA21 targets PA domain II, inhibiting PA63 oligomerization.

Conclusions:

  • The study elucidated the distinct neutralization mechanisms and epitope specificities of hmPA6 and PA21.
  • These antibodies offer promising therapeutic strategies for anthrax.
  • Combination therapy using both antibodies targeting different epitopes may enhance anthrax treatment outcomes.

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