Multivalent VAccines for Biodefense

用于生物防御的多价疫苗

• 批准号: 7739980
• 负责人: MARIANNE MANCHESTER
• 金额: $ 26.11万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739980
• 关键词: Acute; Adjuvant; Adverse effects; Animals; Anthrax antitoxin; Anthrax disease; Antibodies; Antigens; Bontoxilysin; Botulinum Toxin Type A; Chimeric Proteins; Complex; Development; Generations; Goals; Immune response; Immunity; Immunization; Injection of therapeutic agent; Insect Viruses; Intoxication; Mus; Proteins; Rattus; Reagent; Ricin; Ricin A Chain; Surface; Testing; Toxin; Vaccines; Virus-like particle; anthrax lethal factor; anthrax protective factor; anthrax toxin; anthrax toxin receptors; base; biodefense; immunogenicity; in vivo; innovation; mutant; novel; pathogen; public health relevance; recombinant virus; response; vaccine development

DESCRIPTION (provided by applicant): There is an urgent need to develop fast-acting vaccines for biodefense. For pathogens and acute toxins, the ability to rapidly induce immunity with a minimum of adverse effects is of paramount importance. A variety of immunogens from relevant pathogens and toxins have been identified, however numerous immunizations are typically required to induce a protective response. The development of novel adjuvants that boost immune responses without adverse effects is highly desirable. We recently developed a unique reagent that combines the functions of an anthrax antitoxin and vaccine in a single compound. This reagent is based on multivalent display of the anthrax toxin receptor, ANTXR2, on the surface of an icosahedral insect virus. We showed that the recombinant virus-like particles protect rats from anthrax intoxication and that they induce an extremely potent immune response against lethal toxin when coated with anthrax protective antigen (PA). This immune response protects animals against lethal toxin challenge within four weeks after a single administration without the need for adjuvant. The goal of this application is to test whether the utility of this presentation platform can be expanded to display other proteins for which fast-acting vaccines are urgently needed. In particular, we seek to test whether the virus-like particle (VLP) platform can be adapted to generate a rapid and protective immune response to botulinum neurotoxin and ricin toxin. In aim 1 we will generate PA-RTA and PA-BoNT/A fusion proteins and assemble the VLP-based immunogens. In aim 2 we will evaluate the immunogenicity of these complexes in vivo. If the proposed strategy is successful, the application of this platform could be expanded dramatically for development of vaccines against numerous other pathogens. (RTA: ricin toxin A chain; BoNT/A: botulinum neurotoxin A). PUBLIC HEALTH RELEVANCE: There is an urgent need to develop fast-acting vaccines for biodefense. We recently developed a unique reagent that induces a protective immune response against anthrax toxin four weeks after a single injection in the absence of an adjuvant. This reagent is based on multivalent display of the anthrax toxin receptor and anthrax protective antigen on the surface of an icosahedral insect virus. The goal of this proposal is to test whether this presentation platform can be used to display other proteins for which fast-acting vaccines are urgently needed. In particular, we seek to test whether the virus-like particle platform can be adapted to generate a rapid and protective immune response to botulinum neurotoxin and ricin toxin. If the proposed strategy is successful, the application of this platform could be expanded dramatically for development of vaccines against numerous other pathogens.

描述（由申请人提供）：迫切需要开发生物延伸的快速疫苗。对于病原体和急性毒素，迅速诱导免疫力的能力最少至关重要。已经发现了来自相关病原体和毒素的各种免疫原子，但是通常需要进行多种免疫来诱导保护性反应。高度希望增强免疫反应的新型佐剂的发展。我们最近开发了一种独特的试剂，该试剂结合了单个化合物中炭疽抗毒素和疫苗的功能。该试剂基于在二十面体昆虫病毒表面的炭疽毒素受体Antxr2的多价显示。我们表明，重组病毒样颗粒可保护大鼠免受炭疽毒化的影响，并且当用炭疽抗原抗原（PA）涂有涂层时，它们会诱导针对致命毒素的极有效反应。这种免疫反应可保护动物在一次给药后的四个星期内无需辅助剂。该应用程序的目的是测试该演示平台的实用性是否可以扩展，以显示迫切需要快速作用疫苗的其他蛋白质。特别是，我们试图测试是否可以适应病毒样颗粒（VLP）平台，以产生对肉毒肉毒神经毒素和ricin毒素的快速和保护性免疫反应。在AIM 1中，我们将生成PA-RTA和PA-BONT/A融合蛋白，并组装基于VLP的免疫原。在AIM 2中，我们将在体内评估这些复合物的免疫原性。如果提出的策略成功，则可以大幅扩展该平台以针对许多其他病原体开发疫苗。 （RTA：Ricin毒素A链； BONT/A：肉毒杆菌神经毒素A）。公共卫生相关性：迫切需要开发快速效果以进行生物形式。我们最近开发了一种独特的试剂，该试剂在没有佐剂后四周诱导针对炭疽毒素的保护性免疫反应。该试剂基于多价显示炭疽毒素受体和炭疽抗原在二十面体昆虫病毒表面的保护性抗原。该提案的目的是测试该演示平台是否可以用于显示迫切需要快速疫苗的其他蛋白质。特别是，我们试图测试是否可以适应病毒样颗粒平台，以产生对肉毒神经毒素和ricin毒素的快速和保护性免疫反应。如果提出的策略成功，则可以大幅扩展该平台以针对许多其他病原体开发疫苗。