Novel adjuvant to boost humoral and cellular immune responses against influenza

项目摘要/摘要 流感是一种高度传染性的病毒性传染病，造成25万-50万人死亡和300万-500万人死亡 全世界每年都有严重的疾病。细胞免疫对消除病毒感染的细胞和促进 恢复。对保守抗原的细胞免疫也可以保护人们免受流感的侵袭。 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，目前批准用于促进流感疫苗接种的佐剂主要是 增强体液免疫应答，对细胞免疫影响不大。这个项目开发了一种物理 基于射频(RF)的佐剂(RFA)具有强大的体液和细胞佐剂效应以促进流感 接种局部、全身或长期副作用最小的疫苗。我们的初步研究发现了 体液和细胞佐剂非侵入性RF治疗对几种疫苗抗原的影响 模型抗原卵清蛋白、重组血凝素和2009年大流行H1N1疫苗。这个 体液RFA效果相当，细胞RFA效果优于使用的最有效佐剂 流感疫苗。我们假设新的RFA将显著促进流感疫苗诱导的体液 和细胞免疫反应，从而加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效果并描述辅助机制(特定 目标1)；探索RFA以促进季节性和大流行前流感疫苗接种(具体目标2)；制定 以RFA为基础的通用T细胞疫苗(特定目标3)。RFA的安全性和有效性将首先在小鼠身上进行探索 模型，然后在小型猪身上进行验证。该项目的成功将使我们能够提交调查报告 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，用于方便且经济高效的流感疫苗佐剂接种。

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.