Novel Vaccines for Anthrax Prevention

预防炭疽病的新型疫苗

• 批准号: 6772449
• 负责人: david allen steinhauer
• 金额: $ 30.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772449
• 关键词: Bacillus anthracis; Orthomyxoviridae; anthrax toxin; anthrax vaccines; antigen antibody reaction; bacterial antigens; bacterial proteins; bacterial toxins; biotechnology; bioterrorism /chemical warfare; chimeric proteins; drug screening /evaluation; enzyme linked immunosorbent assay; flow cytometry; genetic manipulation; genetic techniques; influenza vaccines; laboratory mouse; microorganism hemagglutinin; receptor binding; vaccine development; vector vaccine; virus protein

DESCRIPTION (provided by applicant): Anthrax is a highly lethal disease caused by Bacillus anthracis. Currently it poses a major concern as a bioterrorist weapon. The three-component toxin of Bacillus anthracis is the principle mediator of pathogenicity. It consists of the protective antigen (PA), the lethal factor (LF), and the edema factor (EF). Although antibody responses to the PA are known to protect anthrax, a suitable vaccine for prevention of inhalation anthrax, the most lethal form, is not currently available for large-scale practical use. We hypothesize that it might be possible to engineer particular domains of the PA into the hemagglutinin glycoprotein (HA) of influenza virus, and that vaccine strains of influenza containing such chimeric HAs might provide protective immunity against both diseases. One advantage is that influenza vaccines are produced in large scale on an annual basis, so mass immunization procedures would not be problematic provided the recombinant viruses grow reasonably well. Another advantage of this approach relates to the properties of influenza as a strong inducer of both systemic and mucosal immunity, and as such, might enhance the neutralizing antibody responses to PA and provide protection against inhalation anthrax. As such, we propose to generate chimeric HA-PA proteins, assess their capacity to provide HA receptor binding and membrane fusion functions, and generate viruses containing the most suitable constructs by reverse genetics. These viruses will then be analyzed in mice for their ability to induce appropriate anti-HA and anti-PA immune responses.

描述（申请人提供）：炭疽是由炭疽杆菌引起的高度致命的疾病。目前，它作为生物恐怖武器引起了人们的主要关注。炭疽杆菌的三组分毒素是致病性的主要介质。它由保护性抗原（PA）、致死因子（LF）和水肿因子（EF）组成。 尽管已知对PA的抗体反应可以保护炭疽，但用于预防吸入性炭疽（最致命的形式）的合适疫苗目前尚未可大规模实际使用。我们推测，有可能将 PA 的特定结构域改造到流感病毒的血凝素糖蛋白 (HA) 中，并且含有这种嵌合 HA 的流感疫苗株可能会提供针对这两种疾病的保护性免疫力。一个优点是流感疫苗每年都可以大规模生产，因此只要重组病毒生长得相当好，大规模免疫程序就不会出现问题。这种方法的另一个优点涉及流感作为全身和粘膜免疫的强诱导剂的特性，因此可能增强对 PA 的中和抗体反应并提供针对吸入性炭疽的保护。因此，我们建议生成嵌合 HA-PA 蛋白，评估其提供 HA 受体结合和膜融合功能的能力，并通过反向遗传学生成包含最合适构建体的病毒。然后将在小鼠中分析这些病毒诱导适当的抗 HA 和抗 PA 免疫反应的能力。

项目成果

The effects of preexisting immunity to influenza on responses to influenza vectors in mice.

• DOI: 10.1016/j.vaccine.2010.06.112
• 发表时间: 2010-08
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: William A. Langley;Konrad C. Bradley;Zhu-Nan Li;G. Talekar;Summer E. Galloway;D. Steinhauer