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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities
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Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities

机译：研制出一种高效的基于牛痘的双重疫苗，用于对抗天花和炭疽这两个重要的生物恐怖实体

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摘要

Bioterrorism poses a daunting challenge to global security and public health in the 21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthrads, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and an-thrax, because of inadequacies associated with each of these vac-cines, serious concerns remain as to the deployability of these vac-cines, especially in the aftermath of a bioterror attack involving these pathogens. We have developed a single vaccine (Wyeth/IL-15/PA) using the licensed Wyeth smallpox vaccine strain that is ef-ficacious against both smallpox and anthrax due to the integration of immune-enhancing cytokine IL-15 and the protective antigen (PA) of B. anthrads into the Wyeth vaccinia virus. Integration of IL-15 renders Wyeth vaccinia avirulent in immunodeficient mice and en-hances anti-vaccinia immune responses. Wyeth/IL-15/PA conferred sterile protection against a lethal challenge of B. anthrads Ames strain spores in rabbits. A single dose of Wyeth/IL-15/PA protected 33% of the vaccinated A/J mice against a lethal spore challenge 72 h later whereas a single dose of licensed anthrax vaccine protected only 10%. Our dual vaccine Wyeth/IL-15/PA remedies the inadequa-cies associated with the licensed vaccines, and the inherent ability of Wyeth vaccinia virus to be lyophilized without loss of potency makes it cold-chain independent thus simplifying the logistics of storage, stockpiling, and field delivery in the event of a bioterror attack involving smallpox or anthrax.
机译：生物恐怖主义对21世纪的全球安全和公共卫生提出了严峻的挑战。天花的主要病原体是天花病毒，炭疽杆菌是造成炭疽的细菌性病原体，它仍处于潜在病原体的顶端，可用于生物恐怖袭击，以造成大量人员伤亡。尽管获得许可的疫苗可用于天花和炭疽疫苗，但是由于每种疫苗的不足之处，这些疫苗的可部署性仍然存在严重问题，尤其是在涉及这些病原体的生物恐怖袭击之后。我们使用许可的Wyeth天花疫苗株开发了一种单一疫苗（Wyeth / IL-15 / PA），由于整合了增强免疫力的细胞因子IL-15和保护性抗原（PA），因此它对天花和炭疽都很有效）的炭疽芽胞杆菌感染了Wyeth牛痘病毒。 IL-15的整合使Wyeth牛痘疫苗在免疫缺陷小鼠中无毒，并增强了抗牛痘疫苗的免疫反应。惠氏/ IL-15 / PA赋予了针对兔炭疽杆菌Ames菌株孢子致死性攻击的无菌保护。单剂量的Wyeth / IL-15 / PA可以在72小时后保护33％的A / J疫苗小鼠免受致命的孢子攻击，而单剂量的许可炭疽疫苗仅能保护10％。我们的双重疫苗Wyeth / IL-15 / PA弥补了许可疫苗的不足之处，并且Wyeth牛痘病毒被冻干的内在能力不会丧失效力，从而使其不依赖冷链，从而简化了存储，库存的后勤工作，以及在涉及天花或炭疽的生物恐怖袭击中进行现场运送。

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  • 作者

    Tod J. Merkel; Pin-Yu Perera; Vanessa K. Kelly; Anita Verma; Zara N. Llewellyn; Thomas A. Waldmann; Joseph D. Mosca; Liyanage P. Perera;

  • 作者单位

    Center for Biologies Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;

    rnVeterans Affairs Medical Center, Washington, DC 20422;

    rnCenter for Biologies Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;

    rnCenter for Biologies Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;

    rnSouthern Research Institute, Birmingham, AL 35255;

    rnMetabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;

    rnJDM Technologies, Ellicott City, MD 21042;

    rnMetabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    biodefense; IL-15; bioterrorism;

    机译：生物防御IL-15;生物恐怖主义;

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