Novel adjuvant to boost humoral and cellular immune responses against influenza

项目总结/摘要 流感是一种传染性极强的病毒性传染病，每年造成25 - 50万人死亡， 全球每年都有严重的疾病。细胞免疫对于消除病毒感染的细胞和促进免疫至关重要。 复苏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 抗原和不良诱导细胞免疫。佐剂有望增强流感疫苗诱导的 体液和细胞免疫应答。然而，目前批准用于加强流感疫苗接种的佐剂主要是 增强体液免疫应答，而对细胞免疫影响较小。这个项目开发了一个物理 基于射频（RF）的佐剂（RFA），具有强效体液和细胞佐剂作用，可增强流感病毒 疫苗接种具有最小的局部、全身或长期副作用。我们的初步研究发现 非侵入性RF治疗对几种疫苗抗原的体液和细胞佐剂效应， 模型抗原卵清蛋白、重组血凝素和2009年大流行性H1N1流感疫苗。的 体液RFA效果相当，细胞RFA效果上级于 流感疫苗。我们假设新型RFA将显著增强流感疫苗诱导的体液免疫。 和细胞免疫应答，从而增加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（特异性 目的1）;探索RFA以促进季节性和大流行前的流感疫苗接种（具体目的2）; 基于RFA的通用T细胞疫苗（具体目标3）。将首先在小鼠中探索RFA的安全性和效力 模型，然后在小型猪中验证。该项目的成功将使我们能够提交研究报告。 设备豁免申请旨在探索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，用于流感疫苗接种的方便和具有成本效益的辅助。

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.