Hwang Hye Suk, Kwon Young-Man, Lee Jong Seok, Yoo Si-Eun, Lee Yu-Na, Ko Eun-Ju, Kim Min-Chul, Cho Min-Kyoung, Lee Young-Tae, Jung Yu-Jin, Lee Ji-Yun, Li Jian-Dong, Kang Sang-Moo
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Antiviral Res. 2014 Oct;110:115-23. doi: 10.1016/j.antiviral.2014.07.016. Epub 2014 Aug 7.
This study demonstrates that immunization with non-replicating virus-like particle (FFG VLP) containing RSV F and G glycoproteins together with RSV F DNA induced T helper type 1 antibody responses to RSV F similar to live RSV infection. Upon RSV challenge 21weeks after immunization, FFG VLP vaccination induced protection against RSV infection as shown by clearance of lung viral loads, and the absence of eosinophil infiltrates, and did not cause lung pathology. In contrast, formalin-inactivated RSV (FI-RSV) vaccination showed significant pulmonary eosinophilia, severe mucus production, and extensive histopathology resulting in a hallmark of pulmonary pathology. Substantial lung pathology was also observed in mice with RSV re-infections. High levels of systemic and local inflammatory cytokine-secreting cells were induced in mice with FI-RSV but not with FFG VLP immunization after RSV challenge. Therefore, the results provide evidence that recombinant RSV FFG VLP vaccine can confer long-term protection against RSV without causing lung pathology.
本研究表明,用含有呼吸道合胞病毒(RSV)F和G糖蛋白的非复制型病毒样颗粒(FFG VLP)与RSV F DNA一起进行免疫接种,可诱导出类似于活RSV感染的针对RSV F的1型辅助性T细胞抗体反应。免疫接种21周后受到RSV攻击时,FFG VLP疫苗接种诱导了对RSV感染的保护作用,表现为肺病毒载量清除、无嗜酸性粒细胞浸润,且未引起肺部病理变化。相比之下,甲醛灭活RSV(FI-RSV)疫苗接种则显示出明显的肺部嗜酸性粒细胞增多、严重的黏液分泌以及广泛的组织病理学变化,导致肺部病理特征明显。在RSV再次感染的小鼠中也观察到了大量的肺部病理变化。RSV攻击后,FI-RSV免疫的小鼠诱导出了高水平的全身和局部炎症细胞因子分泌细胞,而FFG VLP免疫的小鼠则未出现这种情况。因此,这些结果提供了证据,表明重组RSV FFG VLP疫苗可提供针对RSV的长期保护,且不会引起肺部病理变化。