Stable Micronized Vaccines Against Smallpox and Japanese Encephalitis

针对天花和日本脑炎的稳定微粉化疫苗

基本信息

批准号：
7487890
负责人：
Victor Bronshtein
金额：
$ 44.6万
依托单位：
UNIVERSAL STABILIZATION TECHNOLOGIES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-15 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7487890
关键词：
Agreement American Animal Model Animals Anthrax disease Antibiotics Antibodies Antibody Formation Antidotes Antitoxins Antiviral Agents Applications Grants Area Asia Attention Attenuated Attenuated Live Virus Vaccine Attenuated Vaccines Australia Bacteria Biological Biological Assay Biological Preservation Biological Warfare Bioterrorism Bovine Spongiform Encephalopathy Breathing Capsid Proteins Case Fatality Rates Case Study Categories Cells Chemicals Chick Embryo Child ChimeriVax Clinical Cold Chains Collaborations Complex Condition Contracts Cost Savings Country Cowpox virus Culicidae Cytotoxic T-Lymphocytes Developing Countries Development Disease Dose Drug Formulations Ectromelia Effectiveness Emergency Situation Encephalitis Endemic Diseases Engineering Ensure Epidemic Excision Fibroblasts Flavivirus Fluorocarbons Freeze Drying Freezing Genes Genomics Glycoproteins Goals Government Health Professional High temperature of physical object Host Defense Human Immune response Immunity Immunization Immunodeficient Mouse In Vitro Incidence Infection Injectable Injection of therapeutic agent Intramuscular Intraperitoneal Injections Japanese Encephalitis Japanese Encephalitis Vaccines Licensing Life Liquid substance Logistics Measures Methods Modified Vaccinia Virus Ankara Monkeypox Morbidity - disease rate Mus National Institute of Allergy and Infectious Disease Needles Neomycin Neonatal Neurologic Nose Oils Oral Orthopoxvirus PTPN11 gene Particle Size Personal Satisfaction Persons Pharmaceutical Preparations Phase I Clinical Trials Phase II Clinical Trials Phase III Clinical Trials Poxviridae Preparation Prevention Preventive Principal Investigator Process Production Protocols documentation RNA RNA Viruses Range Rate Refrigeration Research Personnel Resources Route Safety Saline Seeds Serial Passage Shipping Ships Smallpox Smallpox Vaccine Smallpox Viruses Solutions Standards of Weights and Measures Sterility Structural Protein Subcutaneous Injections Survivors System Technology Temperature Terrorism Testing Therapeutic Tick-Borne Encephalitis Time Today Toxin Transportation Tularemia United States Food and Drug Administration United States National Institutes of Health Vaccination Vaccine Production Vaccines Vaccinia Vaccinia virus Vial device Viral Proteins Virus Virus Replication Water Week West Nile virus Work Yellow Fever biodefense cold temperature cost day design immunogenic immunogenicity indicated prevention lot production member mortality mouse model nervous system disorder neutralizing antibody new technology novel strategies novel vaccines pathogen programs psychologic reconstitution research study response theories tissue culture tool vaccine efficacy vaccine evaluation vaporization vector control vector vaccine

项目摘要

DESCRIPTION (provided by applicant): Smallpox was one of the most important causes of morbidity and mortality worldwide through the first half of the 20th Century. Smallpox is a potential agent of bioterrorism; it has been designated as Category A Priority Pathogen. Despite the declaration of smallpox eradication in 1980, the existence of variola stockpiles and the threat of bioterrorism demand that immunity to smallpox through vaccination be maintained. In recent years, mosquito-borne infections are reemerging or emerging worldwide at an alarming rate. Japanese Encephalitis is a potential agent of bioterrorism; it has been designated as Category C Priority Pathogen. There are no licensed antiviral drugs against JE and only experimental treatments exist for smallpox. Therefore, vaccination and vector control are the only effective preventive tools, with vaccination being the most cost-effective strategy. Because of this effective protection of people requires immediate application of the countermeasures against these pathogens. Therefore, local storage of the countermeasures is preferable to ensure the greatest efficiency in combating the pathogens and to rapidly stop their spread. The best scenario could be achieved if local health professionals and emergency personal had convenient locally available supplies of vaccines that obviate the need for cold to ensure stability during storage. In the past few years, one of our two collaborating groups, the Group of Dr. Thomas Monath at Acambis has developed a new vaccine against Smallpox (Modified Vaccinia Ankara (MVA) and Japanese Encephalitis (ChimeriVax-JE live, attenuated chimeric vaccine). Both products are in clinical development under Food and Drug Administration (FDA) approved INDs. Both are live, attenuated vaccines and as such are susceptible to thermal degradation; hence, the vaccines must be kept refrigerated. During the past few years, the second of our two collaborating groups, Universal Stabilization Technologies (LIST), under the direction of Dr. Victor Bronshtein, has developed exciting new technologies for stabilizing bacteria and other live products. These technologies eliminate the damaging effects of conventional freeze-drying and allow the preparation of a live product that is stable at ambient temperature, eliminating the need for a cold chain. The objective of this grant proposal is to apply the novel technologies for stabilization developed at LIST to the manufacture of micronized ambient temperature stable MVA smallpox vaccine and ChimeriVax JE vaccine. Such formulated vaccines potentially could be delivered without need for reconstitution using transdermal, oral, nasal or inhalation delivery routes. During the first year our target will be vaccines that maintain high viability and potency after drying and subsequent storage at ambient temperatures. Working in collaboration, the Acambis and LIST will culture the vaccines, explore various ambient temperature stabilization approaches, confirm the stability and potency of the preserved vaccine, and test the immunogenicity and efficacy of the preserved vaccine using the mouse model.

描述（由申请人提供）：天花是20世纪上半叶全球发病和死亡率的最重要原因之一。天花是生物恐怖主义的潜在药物。它已被指定为优先病原体。尽管在1980年宣布了天花的根除，但存在Variola库存的存在以及生物恐怖主义的威胁要求通过疫苗接种免疫天花。近年来，蚊子传播的感染正在以惊人的速度重新出现或出现。日本脑炎是生物恐怖主义的潜在药物。它已被指定为C类优先病原体。没有针对JE的许可抗病毒药，只有天花的实验治疗。因此，疫苗接种和媒介控制是唯一有效的预防工具，疫苗接种是最具成本效益的策略。由于对人的有效保护需要立即针对这些病原体应用对策。因此，优选的对策的本地存储是确保对病原体打击并迅速停止其扩散的最大效率。如果当地的卫生专业人员和紧急个人个人有方便的当地疫苗供应，可以消除需要冷的需要以确保存储期间的稳定性，则可以实现最好的情况。在过去的几年中，阿卡比斯（Acambis）的托马斯·莫纳斯（Thomas Monath）博士组之一是针对天花（改良的疫苗Ankara（MVA）和日本脑炎（Chimerivax-Je Live Live Live Live Live，Santensed Chimeric疫苗）开发了一种新的疫苗。这两种产品都在食品和药物管理下的临床开发（FDA）批准的IND。我们的两个合作群体，即维克多·布朗什（Victor Bronshtein）博士的指导，普遍稳定技术（列表）开发了令人兴奋的新技术，以稳定细菌和其他实时产品。在环境温度下保持稳定的活品，消除了对冷链的需求。。可能会使用透皮，口服，鼻或吸入式途径进行这种配制的疫苗，而无需重组。在第一年，我们的目标将是在环境温度下干燥和随后存储后保持高活力和效力的疫苗。 Acambis和列表合作，将培养疫苗，探索各种环境温度稳定方法，确认保留疫苗的稳定性和效力，并使用小鼠模型测试保留疫苗的免疫原性和功效。