Preclinical development of a vaccine for Nipah virus

尼帕病毒疫苗的临床前开发

• 批准号: 10214949
• 负责人: Thomas William Geisbert
• 金额: $ 141.6万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-11 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10214949
• 关键词: Advanced Development; Aman; Animals; Awareness; Bangladesh; Biological Assay; Biological Markers; Biological Response Modifier Therapy; Biotechnology; COVID-19 pandemic; Case Fatality Rates; Category C pathogen; Cells; Centers for Disease Control and Prevention (U.S.); Cluster randomized trial; Collaborations; Complement; Containment; Data; Development; Disease; Disease Outbreaks; Dose; Ebola; Ebola Hemorrhagic Fever; Ebola virus; Effectiveness; Encephalitis; Epidemic; European Union; Fatality rate; Fever; Funding; GTP-Binding Proteins; Glycoproteins; Government Agencies; Guinea; Health Personnel; Henipavirus; Human; Human Resources; Immunity; India; Infection; Injections; Laboratories; Lassa virus; Lead; Lung diseases; Malaysia; Mammals; Marburgvirus; Methods; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Nature; Nipah Virus; Oryctolagus cuniculus; Pathogenicity; Pathologic; Pharmaceutical Preparations; Pharmacologic Substance; Positioning Attribute; Preventive vaccine; Process; Publications; Recombinant Vaccines; Recombinants; Recording of previous events; Regulatory Affairs; Reporting; Research; Research Personnel; Safety; Singapore; Stomatitis; Toxicology; United States Food and Drug Administration; United States National Institutes of Health; Vaccination; Vaccines; Vesicular stomatitis Indiana virus; Viral Vaccines; Virus; Virus Diseases; Work; World Health Organization; Zoonoses; animal rule; base; cell bank; experience; improved; manufacturing process; medical countermeasure; meetings; mortality; nervous system disorder; neurotoxicity; nonhuman primate; open label; pandemic disease; pathogen; phase I trial; preclinical development; prevent; priority pathogen; product development; programs; research and development; respiratory pathogen; transmission process; vaccine development; vaccine evaluation; vaccine safety; vaccine-induced antibodies; vector vaccine

PROJECT SUMMARY/ABSTRACT Nipah virus (NiV) causes febrile encephalitis and severe respiratory disease in humans with fatality rates as high as 100% in some outbreaks (average ~ 75% for outbreaks over the last decade). There are currently no licensed vaccines or therapies for combating NiV disease. NiV is classified as a Biosafety Level (BSL)-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. In addition to causing morbidity and mortality as a naturally acquired infection, NiV is also categorized as a Category C priority pathogen by several US Government agencies because of the concern for deliberate misuse. Importantly, NiV was recently included on the World Health Organization’s (WHO) 2018 List of Priority Pathogens. As a result of the unprecedented global pandemic of COVID-19 there is heightened concern and awareness regarding respiratory pathogens. Consequently, in March of 2020 the US CDC recommended that NiV be added to the list of Tier 1 Select Agents. Studies to develop effective countermeasures have been hampered by the highly pathogenic nature of NiV and its restriction to BSL-4 containment. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks and with laboratory workers engaged in research. A vaccine based on recombinant G protein deleted (ΔG) vesicular stomatitis virus (rVSVΔG) pseudotyped with the glycoproteins (GP) of a number of high consequence viruses have been shown to completely protect nonhuman primates (NHP) against Ebola, Marburg, and Lassa viruses. In addition, the effectiveness of a rVSV-vectored vaccine in preventing Ebola virus disease was demonstrated in a ring vaccination, open-label, cluster-randomised trial in Guinea during the 2013-16 Ebola epidemic. This vaccine was recently licensed as ERVEBO by the European Union and US FDA. Recently, we developed replication-restricted rVSV NiV vaccine vectors expressing the NiV glycoproteins. Importantly, we showed that these vaccines can completely protect NHPs against high dose lethal NiV Bangladesh strain challenge when used as single injection vaccines. This new data is critically important in the context of containing outbreaks as the most effective vaccine in containing a respiratory pathogen and preventing a pandemic is a vaccine that works rapidly with a single administration. Development of a replication restricted platform that provides improved safety without compromising efficacy is a highly significant advancement and can be applied to other viruses with pandemic potential. The main objective of this proposal is to develop a rVSV-based vaccine against NiV (rVSV-NiVBG) that can provide both rapid protection and long term immunity against the most prevalent and pathogenic Bangladesh strain of NiV and to identify biomarkers that can be used to predict protection. In regard to product development, work will also be done to generate research cell bank (RCB) and viral vaccine bank (RVB), a manufacturing process, and conduct of GLP-safety toxicology.

项目总结/文摘