Hwang Hye Suk, Lee Young-Tae, Kim Ki-Hye, Ko Eun-Ju, Lee Youri, Kwon Young-Man, Kang Sang-Moo
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Virology. 2017 Nov;511:142-151. doi: 10.1016/j.virol.2017.08.022. Epub 2017 Aug 29.
Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia.
福尔马林灭活呼吸道合胞病毒（FI-RSV）疫苗接种会导致儿童在接触RSV后出现疫苗增强型呼吸道疾病（ERD）。已知呈现RSV F融合蛋白的病毒样颗粒（F VLP）可增强1型辅助性T细胞（Th1）免疫反应，并在动物模型中避免ERD。我们推测，F VLP会引发免疫反应，在随后接触易引发ERD的FI-RSV时预防ERD。在此，我们证明，对小鼠进行异源F VLP初免并用FI-RSV加强免疫，可在RSV攻击时预防FI-RSV疫苗增强的肺部炎症和嗜酸性粒细胞增多。F VLP初免使肺T细胞转向产生Th1细胞因子的效应性CD8 T细胞，并显著抑制肺部Th2细胞因子。这项研究表明，RSV F VLP初免会调节并改变免疫反应，以应对随后接触易引发ERD的FI-RSV疫苗和RSV感染，抑制Th2免疫介导的肺部组织病理学变化和嗜酸性粒细胞增多。
