A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo

Peng, Jingyi; Wu, Jiaguo; Shi, Ning; Xu, Hua; Luo, Longlong; Wang, Jing; Li, Xinying; Hu, Xiao; Feng, Jie; Li, Xia; Chai, Limin; Qiao, Chun‐Feng

doi:10.3389/fimmu.2022.831536

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…До некоторого времени таких антител было только два -D6F10 и A7C4, и оба антитела не применялись в клинической практике. Сравнительно недавно появилось сообщение о том, что на основе мышиного моноклонального антитела 10D8 группе авторов [24] удалось получить гуманизированное антитело S008, которое рассматривается как кандидатный препарат для клинического применения. Использование МкАт в концентрации 100 нг/мл обеспечивало полную защиту клеток линий Jurcat и Vero от токсического воздействия абрина.…”

Section: биологическая безопасность и защита от биологических угроз B...unclassified

Humanized Antibodies. Modern Developments and Prospects for the Creation of Medical Protectors Against Biological Threads and Hazards

Gorshkov,

Pechenkin,

Kuznetsovskiy

et al. 2024

jour

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Passive immunization is the variant of the immunization, in which antibodies are introduced into the body in quantities, sufficient to provide a therapeutic effect. One of the «windows of opportunity» for passive immunization is an urgent post-exposure prophylaxis of infectious diseases and their preventive therapy, especially in the absence of chemotherapy drugs suitable for these purposes or their insufficient effectiveness. The existing heterologous drugs based on hyperimmune sera are highly reactogenic, and obtaining donor human immunoglobulins is associated with a number of ethical and technical restrictions. Therefore, biotechnologies that make it possible to obtain, on an industrial scale, low-reactogenic preparations of chimeric monoclonal antibodies with partially human specificity, as well as recombinant antibodies with fully human specificity, have enormous prospects. This trend is called «humanization of antibodies.» The purpose of this article is to analyze modern developments and to show the prospects for creating humanized antibodies specific to antigens of pathogens of especially dangerous infections and toxins as medical biological protection agents. The sources of the research are English-language studies and the scientific literature available via the Internet. The research method is an analysis of scientific sources on the topic being studied from the general to the specific. Results and discussion. The history of the creation of specific prevention drugs based on heterologous and homologous sera/immunoglobulins and monoclonal antibodies is presented. It has been shown in the article, that humanized specific monoclonal antibodies are widely used currently for the treatment of a number of severe chronic diseases (for example, rheumatoid arthritis, psoriasis, immunoinflammatory bowel diseases, malignant tumors). Conclusion. Recently, there has been an increase in numbers of both scientific research and developments, and drugs of recombinant antibodies already approved for use in clinical practice, specific to antigens of pathogens of especially dangerous infections and toxins - potential agents of bioterrorism, such as the anthrax microbe, botulinum toxins of various types, plant toxins ricin and abrin, ebolaviruses, coronaviruses. Such drugs can also be used as medical protectors against biological threats and hazards.

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Section: биологическая безопасность и защита от биологических угроз B...unclassified

Humanized Antibodies. Modern Developments and Prospects for the Creation of Medical Protectors Against Biological Threads and Hazards

Gorshkov,

Pechenkin,

Kuznetsovskiy

et al. 2024

jour

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“…В условиях in vivo авторы использовали абрин в дозе 0,25 мг/кг, обеспечивающий гибель 100 % мышей, взятых в опыт. Введение лабораторным животным антител в дозе 50 мкг/кг обеспечило 100 % выживаемость на фоне введения абрина в дозе 0,25 мг/кг [35].…”

Section: биологическая безопасность и защита от биологических угрозunclassified

Ricin and Abrin as Possible Agents of Bioterror

Pechenkin,

Gorshkov,

Sablina

et al. 2022

jour

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Plant toxins – ricin and abrin, obtained in a purified form from the beans of the castor bean and Abrus precatorius respectively, are considered by Western experts as potential damaging agents of a biological nature. The purpose of this work is to consider the danger of using ricin and abrin as agents of biological terrorism, as well as to assess the existing approaches and means for identifying these toxins, treating the intoxication caused by them, as well as the level of development of vaccine preparations. Both toxins have a similar molecular structure and mechanism of action. They consist of two subunits – A and B, resistant to high temperatures and extreme pH values. The mechanism of their damaging action is based on irreversible inhibition of the process of protein synthesis. The LD50 of ricin for humans, according to various sources, is 3 µg/kg for inhalation and intravenous intake, 22–25 µg/kg for enteral intake, and about 500 µg/kg for subcutaneous intake. Abrin is more toxic than ricin, with an LD50 for humans ranging from 0.1 µg/kg to 1 µg/kg depending on the route of entry. In case of enteral poisoning with ricin and abrin, the victims develop symptoms of gastroenteritis within a few hours: nausea, vomiting and pain in the abdominal cavity and chest, diarrhea. Bleeding from various parts of the gastrointestinal tract may be present. In future, general intoxication symptoms (headache, weakness, fever) and symptoms of multiple organ damage (acute renal failure and acute liver failure) develop. In the terminal stage, symptoms of vascular shock and vascular collapse are expressed. Death usually occurs on the third day or later. Cases of the use of ricin and abrin for criminal and terrorist purposes are described in the article. The main approaches and modern means of indication, means of treating ricin and abrine intoxication, as well as the state of development of vaccine preparations are shown. The given data show that the danger of these toxins as damaging agents is underestimated in Russia. It is necessary to develop diagnostic test systems that allow early detection of intoxication with plant toxins in the affected and the toxins themselves on environmental objects, as well as specific means for the treatment and prevention of acute poisoning with ricin and abrin.

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A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo

Cited by 2 publications

References 26 publications

Humanized Antibodies. Modern Developments and Prospects for the Creation of Medical Protectors Against Biological Threads and Hazards

Humanized Antibodies. Modern Developments and Prospects for the Creation of Medical Protectors Against Biological Threads and Hazards

Ricin and Abrin as Possible Agents of Bioterror

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