Cross-Protective Multivalent Vaccine for Tick-Borne Flaviviruses

蜱传黄病毒交叉保护性多价疫苗

基本信息

批准号：
10225429
负责人：
DAVID E CLEMENTS
金额：
$ 87.67万
依托单位：
HAWAII BIOTECH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-06 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10225429
关键词：
Adjuvant Alkhurma Virus Antibodies Antibody titer measurement Antigens Area Biological Assay Biotechnology Canada Categories Cells Clinical Trials Country Cyclic GMP Dengue Virus Development Disease Dose Ensure Europe European Evaluation Family Feedback Flaviviridae Formulation Geographic Distribution Geographic Locations Geography Goals Guidelines Hawaii Hemorrhage Human Human Resources Immune response Immunize India Infection Infectious Diseases Research Insecta International Kyasanur Forest disease virus Medical Middle East Military Personnel Mission Modeling Mus National Institute of Allergy and Infectious Disease Neurologic North America Oryctolagus cuniculus Pathogenicity Phase Population Positioning Attribute Powassan virus Process Protein Subunits Proteins Recombinants Research Research Institute Research Personnel Risk Role Safety Schedule Serum Strategic Planning Switzerland System Technology Testing Texas Tick-Borne Encephalitis Tick-Borne Encephalitis Virus Toxicity Tests Toxicology United States National Institutes of Health Universities Vaccination Vaccine Antigen Vaccine Production Vaccines Virus West Nile virus Work base clinical development emerging pathogen env Gene Products first responder global health hemorrhagic fever virus high risk human pathogen meetings member mosquito-borne neutralizing antibody potency testing preclinical development priority pathogen research clinical testing success tick-borne flavivirus vaccine candidate vaccine development vaccine safety

Adjuvant Alkhurma Virus Antibodies Antibody titer measurement Antigens Area Biological Assay Biotechnology Canada Categories Cells Clinical Trials Country Cyclic GMP Dengue Virus Development Disease Dose Ensure Europe European Evaluation Family Feedback Flaviviridae Formulation Geographic Distribution Geographic Locations Geography Goals Guidelines Hawaii Hemorrhage Human Human Resources Immune response Immunize India Infection Infectious Diseases Research Insecta International Kyasanur Forest disease virus Medical Middle East Military Personnel Mission Modeling Mus National Institute of Allergy and Infectious Disease Neurologic North America Oryctolagus cuniculus Pathogenicity Phase Population Positioning Attribute Powassan virus Process Protein Subunits Proteins Recombinants Research Research Institute Research Personnel Risk Role Safety Schedule Serum Strategic Planning Switzerland System Technology Testing Texas Tick-Borne Encephalitis Tick-Borne Encephalitis Virus Toxicity Tests Toxicology United States National Institutes of Health Universities Vaccination Vaccine Antigen Vaccine Production Vaccines Virus West Nile virus Work base clinical development emerging pathogen env Gene Products first responder global health hemorrhagic fever virus high risk human pathogen meetings member mosquito-borne neutralizing antibody potency testing preclinical development priority pathogen research clinical testing success tick-borne flavivirus vaccine candidate vaccine development vaccine safety

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项目摘要

Project Summary/Abstract The NIH/NIAID 2017 Strategic Plan is specifically directed at promoting research that can provide solutions to mitigate the threat posed by emerging and re-emerging diseases. The tick-borne flavivirus (TBFV) group includes a number of important human pathogens that result in serious neurological or hemorrhagic diseases that are either Category B or C priority pathogens. The TBFVs are considered to be emerging or re-emerging pathogens due to increases in the number of human infections, the expansion of their geographic distribution, and emergence of new viruses. Additionally, the number of different viruses in the TBFV group poses challenges. There are two licensed Tick-borne encephalitis virus (TBEV) vaccines in Europe. These vaccines are based on the European strains of TBEV (TBEV-Eu), and while they provide some level of cross-neutralization, not all of the TBFV are covered. Furthermore, these vaccines are not licensed in the U.S. and are no longer available in Canada. The development of a multivalent vaccine that provides cross-protection against multiple pathogenic TBFVs would be of great value and is in line with the priorities of NIH/NIAID to develop multivalent and cross-protective technologies. We have demonstrated that two combinations of TBFV recombinant envelope subunit proteins (r80E) can provide protection against a diverse range of TBFV in a mouse challenge model. Additionally, passive transfer studies using serum from mice immunized with combinations of the r80E protein confirm the role of antibodies in protection against virus challenge. This Phase IIB application builds upon our initial efforts to develop a multivalent TBFV vaccine that provides broad cross-protection against viruses in this group. The proposed research aims to 1) optimizing the vaccine formulation; 2) produce pilot lots of the antigens; 3) conduct a pre-IND meeting with the FDA; and 4) conduct potency and toxicity testing to establish the suitability and safety of the final TBFV vaccine formulation. With the successful completion of these efforts, we will be positioned to advance a multicomponent TBFV vaccine into a cGMP manufacturing campaign and toward clinical evaluation.

项目摘要/摘要 NIH/NIAID 2017战略计划专门针对促进可以提供的研究解决新兴和重新出现疾病所构成的威胁的解决方案。 tick传播的黄病毒（TBFV）组包括许多重要的人类病原体，这些病原体导致严重的神经系统或是B类或C优先病原体的出血性疾病。 TBFV被认为是由于人类感染的数量增加，新兴或重新出现的病原体，它们的地理分布和新病毒的出现。此外，不同病毒的数量 TBFV组提出了挑战。有两种有执照的tick传播脑炎病毒（TBEV）疫苗欧洲。这些疫苗基于欧洲TBEV（TBEV-EU）的菌株，同时它们提供一定程度的交叉中和化，并非所有TBFV都涵盖。此外，这些疫苗不是在美国获得许可，不再在加拿大获得。多价疫苗的开发针对多种致病性TBFV提供的交叉保护将具有很大的价值，并且与 NIH/NIAID的优先级是开发多价和跨保护技术的优先级。我们已经证明了 TBFV重组信封亚基蛋白（R80E）的两种组合可以提供保护小鼠挑战模型中的TBFV范围多样。此外，使用血清的被动转移研究从与R80E蛋白质组合免疫的小鼠中，抗体在保护中的作用反对病毒挑战。此阶段IIB应用程序是基于我们最初开发多价的最初努力 TBFV疫苗可在该组中针对病毒提供广泛的交叉保护。拟议的研究目的是1）优化疫苗配方； 2）生产大量抗原的飞行员； 3）进行预定与FDA会面； 4）进行效力和毒性测试以确立最终的TBFV疫苗配方。随着这些努力的成功完成，我们将被定位为将多组分TBFV疫苗推向CGMP制造活动并迈向临床评估。