可溶性 F 蛋白在呼吸道合胞病毒攻击后加重疫苗接种后的肺部组织病理学，但在病毒样颗粒上呈现时则不会。
Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles.
机构信息
a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
b Department of Biology Institute for Biomedical Sciences , Georgia State University , Atlanta , GA , USA.
出版信息
Hum Vaccin Immunother. 2017 Nov 2;13(11):2594-2605. doi: 10.1080/21645515.2017.1362514.
Abstract
Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost vaccination of F VLP induced effective protection, prevented infiltration of eosinophils and vaccine- enhanced disease after challenge. This study provides insight into developing an effective and safe RSV vaccine candidate.
摘要
呼吸道合胞病毒（RSV）融合（F）蛋白被认为是一种有保护作用的疫苗靶点，尽管其疗效和安全性仍不甚清楚。我们研究了可溶性 F 蛋白或病毒样颗粒（F-VLP）形式的 F 蛋白的免疫原性、疗效和安全性。F-VLP 优先诱导 IgG2a 抗体和 T 辅助细胞 1（Th1）免疫应答，而 F 蛋白诱导 IgG1 同型和 Th2 应答。尽管在 RSV 攻击前进行了一次或多次疫苗接种以清除肺部病毒，但 F 蛋白免疫的小鼠仍出现体重减轻、肺部组织病理学改变、高黏液产生和嗜酸性粒细胞浸润。相比之下，F-VLP 的一次或多次疫苗接种诱导了有效的保护，防止了挑战后的嗜酸性粒细胞浸润和疫苗增强疾病。本研究为开发有效和安全的 RSV 疫苗候选物提供了思路。
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