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：
10472452
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/10472452
关键词：
Accounting Address Agriculture Ambylomma americanum Animal Model Antibody titer measurement Antigens Asia Asian Categories Cell Culture Techniques Centers for Disease Control and Prevention (U.S.)Connecticut Containment Crimean-Congo Hemorrhagic Fever Virus DNA DNA Viruses Development Disease Electron Microscopy Emerging Communicable Diseases Encephalitis Ensure Funding Generations Genes Geographic state Goals Gold 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 Universities Vaccinated Vaccines Vaccinia virus Vector-transmitted infectious disease Viral Viral Genes Viral Hemorrhagic Fevers Viral Vector Virus Virus Diseases Virus-like particle Western Blotting arthropod-borne base 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-borne vector-induced

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.

项目摘要在美国和世界范围内，Tickborne疾病仍然是公共卫生的重大关注，因为环境和气候变化使得壁虱，壁虱栖息地及其巨大扩展哺乳动物宿主。仅在新英格兰地区，孤星tick虫就在2017年首次报道通过在2018年建立异国亚洲的长角壁虱。最近的一份CDC报告表明从2004年到2016年，美国的Tickborne疾病翻了一番以上，占所有疾病的77％报告了媒介传播疾病。该报告还表明，美国没有充分准备预防和控制这些威胁。许多引起脑炎和出血热的tick病毒在美国，人类特别关心的是，例如重新出现的Powassan病毒（POWV）最近发现的Heartland病毒（HRTV）。亚洲的另一种新兴的tick虫病毒是严重的发烧与血小板减少综合征病毒（SFTSV），与HRTV密切相关，该病毒与HRTV密切相关，该病毒是由亚洲长角tick正在迅速传播，现在在美国12个州出现。一些其他异国情调的tick虫病毒剂引起了美国的关注，包括tick脑炎病毒（TBEV）， OMSK出血热病毒（OHFV）和Crimean-Congo出血热病毒（CCHFV）。更好为这些新兴威胁做准备，我们在（1）疫苗开发方面组成了一支专家康涅狄格大学（2）康涅狄格州农业实验站的Tickborn病毒和（3）在国家新兴传染病实验室中，动物模型在最大生物疗法中并提出四个风险组3（RG3）和RG4 Tickborne的疫苗开发和测试脑炎和出血性发烧病毒分类为NIAID类别A或C优先病原体，并且 WHO在其最新的2018年蓝图蓝图清单中优先考虑需要加速的优先疾病清单研发。我们开发了一种快速的方法来生成离甲状腺病毒（VacV）载体，该载体将使我们能够快速测试许多tick虫病毒基因，以确保保护性的强烈表达病毒样颗粒（VLP）的抗原和分泌。该平台基于金标准的病毒载体（VacV）诱导高水平的体液和细胞介导的免疫反应。这些VACV矢量当用作疫苗时，复制缺陷，但在标准细胞培养中易于传播与其他复制缺陷毒病毒媒介（如MVA）不同，高滴度。我们还将生成DNA- 基于纯种的疫苗和纯化的VLP（作为亚基疫苗），因此三种不同类别的疫苗可以单独或在促进方案中测试候选人的免疫原性。最后，我们将测试使用tick传输动物模型概括增强的疫苗的功效滴答喂食已记录的传输和传播。