Development of a Yellow Fever Vaccine for Vulnerable Population

为弱势群体开发黄热病疫苗

• 批准号: 8056918
• 负责人: Ian James Amanna
• 金额: $ 99.99万
• 依托单位: NAJIT TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056918
• 关键词: Adult; Age; Age-Months; Age-Years; Attenuated; Attenuated Vaccines; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Collaborations; Communities; Consultations; Culicidae; Cyclic GMP; Data; Developing Countries; Development; Disease; Dose; Drug Formulations; Elderly; Emerging Communicable Diseases; Encephalitis; Future; Generations; Growth; Human; Hydrogen Peroxide; Immune; Immunity; In Vitro; Inactivated Vaccines; Incidence; Industry; Infant; Investigation; Life; Military Personnel; Monitor; Morbidity - disease rate; Mus; Nigeria; Oral; Oral Poliovirus Vaccine; Oryctolagus cuniculus; Outcome; Paralysed; Patients; Peru; Phase; Phase I Clinical Trials; Poliomyelitis; Population; Population Heterogeneity; Price; Proteins; Recommendation; Reporting; Resources; Risk; Safety; Schedule; Seeds; Serious Adverse Event; Severe Adverse Event; Small Business Innovation Research Grant; Smallpox; Soldier; System; Technology; Testing; Time; Toxicity Tests; Toxicology; United States; Vaccination; Vaccines; Virus; Vulnerable Populations; Work; World Health Organization; Yellow Fever; Yellow Fever Vaccine; Yellow fever virus; age group; base; design; disability; immunogenic; immunogenicity; improved; in vivo; long term hospitalization; meetings; mortality; nervous system disorder; neurotropic; new technology; nonhuman primate; novel strategies; novel vaccines; pathogen; potency testing; protective efficacy; safety testing; stability testing; vaccine candidate

DESCRIPTION (provided by applicant): Yellow fever virus (YFV) was at one time endemic in the United States and represents a mosquito-borne emerging/re-emerging human pathogen that causes up to 20% mortality. The current live attenuated YFV vaccine was developed in 1936 and following the development of a virus seed lot system, it has not been modified or otherwise improved in over 50 years. According to the CDC, this vaccine causes 47 severe adverse events (defined as resulting in hospitalization, long-term disability, or death) per million vaccinations. More recent reports indicate that vaccine-associated neurological disease occurs at an approximate rate of 1 case per 10,000 vaccinations. YFV vaccination of infants <9 months of age has been contraindicated since the 1960's due to high rates of vaccine-associated encephalitis in this age group. The overall (all ages) mortality rate following YFV vaccination is estimated at 1 to 2 deaths per million doses. More recently, YFV vaccination has been found to cause severe viscerotropic disease in a substantial number of patients >60 years of age (an incidence rate of approximately 1:50,000 doses administered) and these cases result in approximately 50% mortality. This indicates that YFV vaccination is not only contraindicated in infants, but is also not recommended in the elderly due to the increased risk of severe and life-threatening disease. Increased monitoring efforts have also documented several cases of vaccine-related fatalities in young, otherwise healthy adults with no known pre-existing immune deficiencies. There is currently no alternative to live YFV vaccination. In this proposal, we will prepare an inactivated YFV vaccine under GMP conditions and perform the necessary safety, potency, and stability studies required for a future IND submission to the FDA. This vaccine is based on proprietary new technology used to develop inactivated vaccine formulations that can be used to immunize vulnerable populations such as infants and the elderly, in addition to other healthy populations. Preliminary data is provided demonstrating that an H2O2-YFV vaccine is feasible to manufacture, highly immunogenic, and provides full protective immunity against lethal viscerotropic yellow fever. In this project, we will prepare clinical grade vaccine under cGMP conditions, perform in vitro and in vivo safety/toxicity tests, and determine vaccine potency and long-term stability. The successful completion of these objectives will result in cGMP-grade vaccine material suitable for future initiation of a Phase I clinical trial. PUBLIC HEALTH RELEVANCE: In this Phase II proposal, we provide strong preliminary data from our Phase I application demonstrating the antigenicity, immunogenicity, and protective efficacy of a proprietary new vaccine platform that can be used to develop a safer and highly effective YFV vaccine.

描述（由申请人提供）：黄热病病毒（YFV）在美国一次流行，代表了一种蚊子传播/重新出现的人类病原体，可导致高达20％的死亡率。当前的现场衰减YFV疫苗是在1936年开发的，随着病毒种子批次系统的发展，在50多年来未对其进行修改或以其他方式进行改进。根据疾病预防控制中心的说法，该疫苗会导致47种严重的不良事件（定义为导致住院，长期残疾或死亡），每百万疫苗接种。最新的报告表明，与疫苗相关的神经系统疾病的发生率约为每10,000次疫苗的1例。自1960年代以来，由于该年龄段的疫苗相关性脑炎的率很高，因此婴儿的YFV疫苗接种少于9个月。 YFV疫苗接种后的总体（所有年龄）死亡率估计为每百万剂量1至2次死亡。最近，已经发现YFV疫苗接种会导致大量60岁的患者（大约1：50,000剂量的发病率）导致严重的内脏疾病，这些病例大约导致死亡率约50％。这表明YFV疫苗不仅是婴儿禁忌的，而且由于严重和威胁生命的疾病的风险增加，在老年人中也不建议使用。监测工作的增加还记录了几例与疫苗相关的死亡案件，否则健康的成年人却没有已知的免疫缺陷。目前没有其他YFV疫苗接种的选择。在此提案中，我们将在GMP条件下准备灭活的YFV疫苗，并执行未来对FDA的未来IND提交所需的必要安全性，效力和稳定性研究。该疫苗基于专有的新技术，用于开发灭活的疫苗配方，除其他健康人群外，还可以用于免疫弱势群体（例如婴儿和老年人）。提供了初步数据，表明H2O2-YFV疫苗可用于生产，高度免疫原性，并提供全面的保护性免疫，以防止致命的内脏黄热病。在该项目中，我们将在CGMP条件下准备临床级疫苗，在体外和体内安全/毒性测试中进行，并确定疫苗的效力和长期稳定性。这些目标的成功完成将导致CGMP级疫苗材料适合将来开始I期临床试验。 公共卫生相关性：在这一第二阶段提案中，我们提供了I阶段应用中的强大初步数据，这些数据表明了专有的新疫苗平台的抗原性，免疫原性和保护性效能，可用于开发更安全且高效的YFV疫苗。