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.

儿童甲醛暴露后，福尔马林灭活的呼吸道合胞病毒（FI-RSV）疫苗接种导致疫苗增强的呼吸道疾病（ERD）。呈现RSV F融合蛋白（F VLP）的病毒样颗粒可增加T辅助1型（Th1）免疫反应并避免动物模型中的ERD。我们假设F VLP将在随后暴露于易ERD的FI-RSV时引发免疫反应，从而阻止ERD。在这里，我们证明了异源F VLP引发和FI-RSV增强小鼠阻止了RSV攻击后FI-RSV疫苗增强的肺部炎症和嗜酸性粒细胞增多。F VLP引发将肺T细胞重定向至产生Th1细胞因子的效应CD8 T细胞，并显着抑制了肺Th2细胞因子。