Novel adjuvant to boost humoral and cellular immune responses against influenza

增强针对流感的体液和细胞免疫反应的新型佐剂

• 批准号: 9906844
• 负责人: Xinyuan Chen
• 金额: $ 41.03万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906844
• 关键词: Adjuvant; Animal Model; Antibody titer measurement; Antigen-Presenting Cells; Antigens; Body Weight decreased; CD8-Positive T-Lymphocytes; Cells; Cellular Immunity; Cessation of life; Clinic; Communicable Diseases; Cosmetics; Cross Presentation; Cytotoxic T-Lymphocytes; Dendritic Cells; Development; Devices; Electromagnetic Energy; Esthetics; Family suidae; Fluzone; Genes; Goals; H1N1 vaccine; Hemagglutination; Hemagglutinin; Human; Immune response; Immunity; Immunize; Influenza; Influenza A Virus, H1N1 Subtype; Influenza vaccination; Investigation; Lung; MF59; Measures; Mediating; Modeling; Molecular; Mus; Myelogenous; Nucleoproteins; Ovalbumin; Proteins; Readiness; Recombinants; Recovery; Role; Safety; Signal Transduction; Skin; Surface Antigens; T-Lymphocyte; Vaccination; Vaccine Antigen; Vaccines; Viral; Virus; aluminum sulfate; base; chemical reaction; cost effective; immunogenicity; improved; influenza virus vaccine; influenzavirus; mouse model; neutralizing antibody; novel; pandemic disease; pandemic influenza; pre-clinical; protective efficacy; radio frequency; response; side effect; success; vaccine development

Project Summary/Abstract Influenza is a highly contagious viral infectious diseases and causes 250,000-500,000 deaths and 3-5 million severe illnesses each year worldwide. Cellular immunity is crucial to eliminate virus-infected cells and promote recovery. Cellular immunity against conserved antigens can also confer protection against drifted influenza viruses. Current influenza vaccines mainly induce neutralizing antibodies against highly variable surface antigens and poorly induces cellular immunity. Adjuvants are promising to enhance influenza vaccine-induced humoral and cellular immune responses. Yet, current adjuvants approved to boost influenza vaccination mainly enhance humoral immune responses with little effects on cellular immunity. This project develops a physical radiofrequency (RF)-based adjuvant (RFA) with potent humoral and cellular adjuvant effects to boost influenza vaccination with minimal local, systemic or long-term side effects. Our preliminary studies identified potent humoral and cellular adjuvants effects of non-invasive RF treatment on several vaccine antigens, such as model antigen ovalbumin, recombinant hemagglutinin, and pandemic 2009 influenza H1N1 vaccine. The humoral RFA effects are comparable and cellular RFA effects are superior to the most potent adjuvant used in influenza vaccines. We hypothesize the novel RFA will significantly boost influenza vaccine-induced humoral and cellular immune responses, resulting in increased protection against vaccine and non-vaccine viral strains. Three specific aims are proposed: To optimize RFA effects and delineate adjuvantation mechanisms (specific aim 1); To explore RFA to boost seasonal and pre-pandemic influenza vaccination (specific aim 2); To develop RFA-based universal T cell vaccine (specific aim 3). Safety and potency of RFA will be first explored in murine models and then validated in miniature pigs. The success of this project will allow us to submit Investigational Device Exemption applications to explore RFA to boost influenza vaccination in clinics. Our ultimate goal is to develop a handheld RF device for convenient and cost-effective adjuvantation of influenza vaccination.

项目概要/摘要 流感是一种高度传染性的病毒传染病，导致 250,000-500,000 人死亡，3-500 万人死亡 全世界每年都会出现严重疾病。细胞免疫对于消除病毒感染的细胞并促进 恢复。针对保守抗原的细胞免疫也可以提供针对漂移流感的保护 病毒。目前的流感疫苗主要诱导针对高度可变表面的中和抗体 抗原，诱导细胞免疫能力较差。佐剂有望增强流感疫苗诱导的 体液和细胞免疫反应。然而，目前批准的佐剂主要用于加强流感疫苗接种 增强体液免疫反应，对细胞免疫影响很小。该项目开发了一个物理 基于射频 (RF) 的佐剂 (RFA) 具有有效的体液和细胞佐剂作用，可促进流感 疫苗接种具有最小的局部、全身或长期副作用。我们的初步研究确定了有效的 非侵入性射频治疗对多种疫苗抗原的体液和细胞佐剂的影响，例如 模型抗原卵清蛋白、重组血凝素和 2009 年大流行 H1N1 流感疫苗。这 体液 RFA 效果相当，细胞 RFA 效果优于用于治疗的最有效佐剂 流感疫苗。我们假设新型 RFA 将显着增强流感疫苗诱导的体液分泌 和细胞免疫反应，从而增强对疫苗和非疫苗病毒株的保护。 提出了三个具体目标： 优化 RFA 效果并描绘辅助机制（具体 目标1);探索 RFA 以加强季节性和大流行前流感疫苗接种（具体目标 2）；发展 基于 RFA 的通用 T 细胞疫苗（具体目标 3）。 RFA 的安全性和效力将首先在小鼠身上进行探索 模型，然后在小型猪中进行验证。该项目的成功将使我们能够提交研究报告 设备豁免申请探索 RFA 以促进诊所的流感疫苗接种。我们的最终目标是 开发一种手持式射频设备，以方便且经济高效地辅助流感疫苗接种。