展示鞭毛蛋白的病毒样颗粒对诱导针对低免疫原性流感病毒 M2e 蛋白疫苗的 T 辅助型 1 体液和细胞免疫应答具有独特的佐剂效应。
Virus-like particles presenting flagellin exhibit unique adjuvant effects on eliciting T helper type 1 humoral and cellular immune responses to poor immunogenic influenza virus M2e protein vaccine.
机构信息
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States of America.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States of America; Department of Microbiology, Chonnam National University Medical School, Hwasun-gun, Jeonnam 58128, Republic of Korea.
出版信息
Virology. 2018 Nov;524:172-181. doi: 10.1016/j.virol.2018.08.019. Epub 2018 Sep 7.
Abstract
Current licensed adjuvants including aluminum hydroxide (alum) bias immune responses toward T helper type 2 (Th2) immune responses. We tested whether virus-like particles presenting flagellin (Flag VLP) exhibit adjuvant effects on eliciting Th1 type immune responses and improving the efficacy of poor immunogenic tandem repeat M2e (M2e5x) protein vaccine against influenza virus. Co-immunization of mice with Flag VLP and M2e5x protein vaccine induced significantly higher levels of IgG2a isotype (Th1) antibodies in sera and mucosal sites, effector CD4 T cells secreting IFN-γ and granzyme B, and more effective lung viral clearance and protection compared to alum adjuvant. Flag VLP stimulated primary macrophages and dendritic cells to secrete inflammatory cytokines, which is partially dependent on the Toll-like receptor 5. This study provides insight into developing effective vaccine adjuvants.
摘要
目前已获得许可的佐剂包括氢氧化铝（明矾），它们使免疫反应偏向辅助性 T 细胞 2 型（Th2 型）。我们研究了是否可以利用展示鞭毛蛋白（Flag VLP）的病毒样颗粒来引发 Th1 型免疫反应，并提高对流感病毒的低效免疫串联重复 M2e（M2e5x）蛋白疫苗的功效。将 Flag VLP 与 M2e5x 蛋白疫苗共同免疫小鼠，可显著提高血清和黏膜部位 IgG2a 同种型（Th1 型）抗体、分泌 IFN-γ 和颗粒酶 B 的效应性 CD4 T 细胞水平，以及更有效地清除肺部病毒和提供保护，与明矾佐剂相比。Flag VLP 可刺激原代巨噬细胞和树突状细胞分泌炎症细胞因子，这部分依赖于 Toll 样受体 5。本研究为开发有效的疫苗佐剂提供了新视角。
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