Development, Production and Evaluation of a Multivalent Adenoviral Plague Vaccine

多价腺病毒鼠疫疫苗的研制、生产及评价

• 批准号: 7537755
• 负责人: CHRIS LENTZ
• 金额: $ 28.54万
• 依托单位: NORWELL, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-18 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7537755
• 关键词: Academia; Address; Adenovirus Vector; Adenoviruses; Aerosols; Animal Model; Animals; Anthrax disease; Antibody Formation; Antigen Targeting; Antigens; Bacteria; Bioterrorism; Breathing; Budgets; Calcium; Cardiovascular system; Cavia; Class; Clinical Research; Clinical Trials; Communicable Diseases; Data; Dendritic Cells; Development; Dose; Emergency Situation; Ensure; Evaluation; Event; Exposure to; Facility Construction Funding Category; Gene Targeting; Gene Transfer; Guanosine Monophosphate; Housing; Human; Immune; Immune response; Immunity; Immunization; Industry; Infection; Injection of therapeutic agent; Intellectual Property; Intramuscular; Laboratories; Legal patent; Licensing; Medical; Methods; Michigan; Military Personnel; Modeling; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Nature; Organism; Phase; Plague; Plague Vaccine; Pneumonic Plague; Primates; Process; Production; Public Health; Range; Readiness; Recombinants; Research; Research Personnel; Route; Safety; Structural Protein; Study models; System; Technology; Terrorism; Testing; Texas; Therapeutic; Toxic effect; Tularemia; Universities; Vaccination; Vaccines; Vertebral column; Virulent; Work; Yersinia pestis; base; biodefense; cancer immunotherapy; capsule; design; efficacy evaluation; emergency service responder; genetic vaccine; immunogenicity; mortality; neutralizing antibody; nonhuman primate; pathogen; programs; protective effect; response; subcutaneous; success; vector

DESCRIPTION (provided by applicant): The final objective of this effort is to construct and test a multivalent adenoviral vaccine candidate that elicits a potent immune response against Yersinia pestis, the causative agent of plague. The proposed work is a collaborative effort between the University of Texas Medical Branch (UTMB), Norwell, Inc., and Introgen Therapeutics, Inc. The plague vaccine project was selected in response to the growing concern surrounding the organism's use in a potential terrorism event. The NIAID, in response to this threat, has classified the organism as a Class A priority organism. Currently there are no commercially available vaccines for protection from plague in the instance of a bioterrorism event. The lack of a vaccine is particularly worrisome because of the pathogen's capability to inflict widespread morbidity and mortality, upon exposure, to both civilians and military personnel. Project Aims will focus on the development, production and evaluation of a vaccine candidate featuring the low calcium response (LcrV) antigen alone or in combination with two other protective Yersinia pestis antigens Caf1 (F1 capsular antigen) and YscF (a type 3 secretion system structural protein) in an adenoviral vector system. The adenoviral vector system was selected because it not only provides a viable delivery vehicle, but also because of the ability of the vector to elicit an immune response. Both mouse and guinea pig animal models proposed in this study are currently being used at the UTMB for inhalational anthrax and plague, and the aerobiology unit for infecting animals by the aerosol route is in place. We believe this program will provide a valuable first line of defense by deterrence for potential terrorists in search of weapons where no vaccine or treatment option exists. Further, the development of a multivalent adenoviral vaccine is not only significant for biodefense but also for combating global infectious disease. PUBLIC HEALTH RELEVANCE: The objective of this project is to construct and test a multivalent adenoviral vaccine candidate against Yersinia pestis (plague), a Class A priority organism. Currently there is no licensed vaccine for human use to protect against infection with plague despite the pathogen's capability to inflict widespread morbidity and mortality upon exposure to both civilians and military personnel.

描述（由申请人提供）：这项工作的最终目标是构建并测试一种多价腺病毒候选疫苗，该疫苗可引发针对鼠疫病原体耶尔森氏菌的有效免疫反应。拟议的工作是德克萨斯大学医学分部 (UTMB)、Norwell, Inc. 和 Introgen Therapeutics, Inc. 之间的合作成果。选择鼠疫疫苗项目是为了回应人们日益关注该生物体在潜在恐怖主义事件中的使用。为了应对这一威胁，NIAID 已将该生物体列为 A 级优先生物体。目前还没有商业上可用的疫苗来预防生物恐怖主义事件中的鼠疫。缺乏疫苗尤其令人担忧，因为接触该病原体后，平民和军事人员都会造成广泛的发病和死亡。项目目标将重点开发、生产和评估候选疫苗，该疫苗单独使用低钙反应 (LcrV) 抗原，或与其他两种保护性鼠疫耶尔森氏菌抗原 Caf1（F1 荚膜抗原）和 YscF（3 型分泌系统结构抗原）组合使用。蛋白）在腺病毒载体系统中。选择腺病毒载体系统是因为它不仅提供了可行的递送载体，而且还因为该载体能够引发免疫反应。本研究中提出的小鼠和豚鼠动物模型目前正在 UTMB 用于吸入性炭疽和鼠疫研究，并且通过气溶胶途径感染动物的空气生物学单元已经到位。我们相信，该计划将为在没有疫苗或治疗方案的情况下寻找武器的潜在恐怖分子提供威慑作用，提供宝贵的第一道防线。此外，多价腺病毒疫苗的开发不仅对于生物防御具有重要意义，而且对于对抗全球传染病也具有重要意义。公共卫生相关性：该项目的目标是构建和测试针对 A 类优先生物鼠疫耶尔森氏菌（鼠疫）的多价腺病毒候选疫苗。尽管鼠疫病原体在接触到平民和军事人员后能够造成广泛的发病和死亡，但目前还没有获得许可的人类使用疫苗来预防鼠疫感染。