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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：
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.

项目总结