Universal Influenza A/B Vaccine

通用甲型/乙型流感疫苗

基本信息

批准号：
10617390
负责人：
Kenneth C Bagley
金额：
$ 99.89万
依托单位：
ORLANCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-07 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10617390
关键词：
Antibodies Antibody Response Antigen-Presenting Cells Antigens Body Weight decreased Cells Clinical Clinical Trials Companions DNA DNA Vaccines DNA delivery Data Development Devices Dose Electroporation Engineering Exhibits Ferrets Formulation Gold Human Humoral Immunities Immune Immune response Immunologics Inflammation Inflammatory Response Influenza Influenza A virus Influenza B Virus Injections Liquid substance Lung Macaca Macaca fascicularis Macaca mulatta Modeling Mucosal Immune Responses Mucous Membrane Mus Pathogenesis Phase Population Pre-Clinical Model Preclinical Testing Predisposition Publishing Reagent Reporting Role Safety Site Skin Small Business Innovation Research Grant Strategic Planning Syringes T cell response T-Lymphocyte Testing Toxic effect United States National Institutes of Health Vaccinated Vaccination Vaccine Antigen Vaccines Viral Viremia Virus Virus Replication design experience gene gun immunogenicity influenza virus strain influenzavirus innovation next generation nonhuman primate novel particle pre-clinical protective efficacy response safety assessment universal influenza vaccine unvaccinated vaccine delivery vaccine development vaccine evaluation

项目摘要

Abstract Universal influenza vaccines should be possible if conserved antigens of influenza are effectively targeted and effective antiviral immune responses are generated against those antigens. DNA vaccination is an appealing approach for delivering universal influenza vaccines, however, natural immune responses to conserved influenza antigens are typically weak and most DNA vaccines tested in humans have not elicited robust humoral immunity. To overcome the obstacles to developing universal influenza DNA vaccines, we are using novel composite immunogens and delivering them with a next generation Gene Gun device that combines several engineering and formulation innovations that increase immunogenicity by increasing the number of skin cells and antigen presenting cells expressing vaccine antigen. We have already obtained encouraging results with a universal influenza A (UFluA) DNA vaccine. Under this SBIR proposal, we intend to test a companion universal influenza B (UFluB) DNA vaccine to create a more comprehensive universal A/B vaccine (UFluA/B) that will provide broad protective coverage from all influenza A and B types capable of infecting humans. If we are successful at demonstrating that a single UFluA/B DNA vaccine can induce broad responses and protection in mice in the phase I effort, we will advance this this product to preclinical testing under the phase II portion of this application where we will investigate immunogenicity and protective efficacy in naïve and pre-immune ferrets and safety and efficacy in a nonhuman primate model that closely resembles humans in their dosing, immune response to DNA vaccination and susceptibility to influenza. If successful, these data will provide Orlance with a strong preclinical IND data package to advance this strategy to phase I human clinical trials. 2

抽象的如果有效靶向影响力的保守抗原，则可以使用普遍影响疫苗对这些抗原产生有效的抗病毒免疫反应。 DNA疫苗接种是一种外观但是，提供普遍影响疫苗的方法，但是，天然免疫再次构成影响抗原通常弱，大多数在人类中测试的DNA疫苗都没有引起强大的体液免疫学。为了克服开发通用影响力DNA疫苗的障碍，我们正在使用新型的复合材料免疫原子并使用下一代基因枪装置交付它们，该装置结合了几种工程并通过增加皮肤细胞和抗原的数量来提高创新，从而增加免疫原性表达疫苗抗原的细胞。我们已经通过通用获得了令人鼓舞的结果影响力（UFLUA）DNA疫苗。根据该SBIR提案，我们打算测试伴侣普遍影响力 B（UFLUB）DNA疫苗，以创建更全面的通用A/B疫苗（UFLUA/B），该疫苗将提供广泛所有影响力的保护性覆盖范围能够感染人类。如果我们成功证明单一的UFLUA/B DNA疫苗可以在小鼠中引起广泛的反应和保护第一阶段的努力，我们将在本应用程序的第二阶段部分将该产品推向临床前测试我们将在其中研究幼稚和免疫前雪貂和安全性的免疫原性和保护效率在非人类私人模型中的功效，与人类在剂量中与DNA的免疫反应非常相似疫苗接种和对影响力的易感性。如果成功的话，这些数据将为明显的临床前提供正常 IND数据包将该策略推向I期人类临床试验。 2