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Vaccines for Prevention of RG3 and RG4 Emerging Tickborne Viral Diseases

用于预防 RG3 和 RG4 新出现蜱传病毒性疾病的疫苗

基本信息

批准号：
10673195
负责人：
PAULO H VERARDI
金额：
$ 49.94万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-20 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10673195
关键词：
Acceleration Accounting Address Agriculture Ambylomma americanum Animal Model Antibody titer measurement Antigens Asia Asian Categories Cell Culture Techniques Connecticut Containment Crimean-Congo Hemorrhagic Fever Virus DNA Development Disease Electron Microscopy Emerging Communicable Diseases Encephalitis Ensure Funding Generations Genes Goals Habitats Haemaphysalis longicornis Heartland virus Human Immune response Immunocompetent Infectious Diseases Research Interferon Receptor Investigation Knockout Mice Label Laboratories Modeling Mus National Institute of Allergy and Infectious Disease New England Omsk hemorrhagic fever virus Orthobunyavirus Play Powassan virus Prevention Public Health Regimen Reporting Risk Serum Severe Fever with Thrombocytopenia Syndrome Virus Subunit Vaccines Testing Tick-Borne Diseases Tick-Borne Encephalitis Tick-Borne Encephalitis Virus Ticks US State Universities Vaccinated Vaccines Vaccinia virus Vector-transmitted infectious disease Viral Viral Genes Viral Hemorrhagic Fevers Viral Vector Virus Virus Diseases Virus-like particle Visualization Western Blotting arthropod-borne cell mediated immune response climate change cross immunity design efficacy testing environmental change experimental study hemorrhagic fever virus immunogenicity mouse model neutralizing antibody poxvirus vectors prevent priority pathogen protein expression rapid technique research and development tick feeding tick transmission tick-borne tick-borne flavivirus tick-borne virus transmission process vaccine candidate vaccine development vaccine efficacy vaccine evaluation vaccinia virus vector vector induced virus classification

项目摘要

PROJECT SUMMARY Tickborne illnesses continue to be a significant public health concern in the US and worldwide, as environmental and climate changes have allowed the dramatic expansion of ticks, tick habitats, and their mammalian hosts. In the New England region alone, Lone Star ticks were first reported in 2017, followed by the establishment of exotic Asian longhorned ticks in 2018. A recent CDC report indicates that tickborne diseases in the US have more than doubled from 2004 to 2016, accounting for 77% of all reported vector-borne diseases. The report also indicates that the US is not fully prepared to prevent and control these threats. A number of tickborne viruses that cause encephalitis and hemorrhagic fever in humans are of particular concern in the US, such as the re-emerging Powassan virus (POWV), as well as the recently discovered Heartland virus (HRTV). Another emerging tickborne virus in Asia is severe fever with thrombocytopenia syndrome virus (SFTSV), closely related to HRTV, which is transmitted by the Asian longhorned tick that is spreading rapidly and is now present in 12 US states. A number of additional exotic tickborne viral agents are of concern to the US, including tickborne encephalitis virus (TBEV), Omsk hemorrhagic fever virus (OHFV), and Crimean-Congo hemorrhagic fever virus (CCHFV). To better prepare for these emerging threats, we assembled a team of experts in (1) vaccine development at the University of Connecticut, (2) tickborne viruses at the Connecticut Agricultural Experiment Station, and (3) animal models in maximum biocontainment at the National Emerging Infectious Diseases Laboratories and propose the development and testing of vaccines for four Risk Group 3 (RG3) and RG4 tickborne encephalitis and hemorrhagic fever viruses classified as NIAID Category A or C Priority Pathogens, and prioritized by the WHO under its most recent 2018 Blueprint list of priority diseases in need of accelerated research and development. We developed a rapid method to generate vaccinia virus (VACV) vectors that will allow us to quickly test a number of tickborne viral genes to ensure robust expression of protective antigens and secretion of virus-like particles (VLPs). This platform is based on a gold-standard viral vector (VACV) that induces high levels of humoral and cell-mediated immune responses. These VACV vectors are replication-defective when administered as a vaccine, yet easy to propagate in standard cell culture at high titers, unlike other replication-defective poxvirus vectors such as MVA. We will also generate DNA- based vaccines and purified VLPs (as a subunit vaccine), so that three different classes of vaccine candidates can be tested for immunogenicity, either alone or in prime-boost regimens. Finally, we will test the efficacy of the vaccines using tick-transmission animal models to recapitulate the enhancement of transmission and dissemination that has been documented by tick feeding.

项目摘要蜱传疾病仍然是美国和世界范围内的一个重大公共卫生问题，环境和气候变化使得蜱虫、蜱虫栖息地及其哺乳动物宿主仅在新英格兰地区，孤独星星蜱虫于2017年首次报告，在2018年建立了亚洲长角蜱。CDC最近的一份报告显示，从2004年到2016年，美国的蜱传疾病增加了一倍多，占所有蜱传疾病的77%。报告的病媒传播疾病。报告还指出，美国没有做好充分准备，控制这些威胁。一些蜱传病毒引起脑炎和出血热，在美国，人类尤其受到关注，例如重新出现的Powassan病毒（POWV），以及最近发现的心脏地带病毒（HRTV）。亚洲另一种新出现的蜱传病毒是严重发烧血小板减少综合征病毒（SFTSV），与HRTV密切相关，由亚洲长角扁虱，正在迅速传播，目前存在于美国12个州。多个附加外来的蜱传病毒因子是美国所关注的，包括蜱传脑炎病毒（TBEV），鄂木斯克出血热病毒（OHFV）和克里米亚-刚果出血热病毒（CCHFV）。更好地为应对这些新出现的威胁，我们组建了一个专家小组，负责（1）疫苗开发，康涅狄格大学，（2）康涅狄格州农业实验站的蜱传病毒，以及（3）国家新发传染病实验室最大限度生物隔离中的动物模型并建议为四种风险组3（RG 3）和RG 4蜱传疫苗的开发和测试，被归类为NIAID A类或C类优先病原体的脑炎和出血热病毒，以及世卫组织根据其最新的2018年蓝图清单，优先考虑需要加速治疗的优先疾病。研发的我们开发了一种快速产生牛痘病毒（VACV）载体的方法，将使我们能够快速测试一些蜱传病毒基因，以确保保护性基因的稳健表达。抗原和病毒样颗粒（VLP）的分泌。这个平台是基于一个黄金标准的病毒载体（VACV），其诱导高水平的体液和细胞介导的免疫应答。这些VACV载体当作为疫苗施用时是复制缺陷型的，但在标准细胞培养物中易于繁殖，更高滴度，不像其他复制缺陷型痘病毒载体如MVA。我们也会生成DNA- 的疫苗和纯化的VLP（作为亚单位疫苗），因此三种不同类型的疫苗可以单独或在初免-加强方案中测试候选物的免疫原性。最后，我们将测试使用蜱传播动物模型来概括疫苗的功效，传播和传播已被记录的蜱喂养。