Han Junyan, Takeda Katsuyuki, Wang Meiqin, Zeng Wanjiang, Jia Yi, Shiraishi Yoshiki, Okamoto Masakazu, Dakhama Azzeddine, Gelfand Erwin W
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
Am J Respir Cell Mol Biol. 2014 Jul;51(1):143-54. doi: 10.1165/rcmb.2013-0360OC.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illnesses in infants worldwide. Both RSV-G and RSV-F glycoproteins play pathogenic roles during infection with RSV. The objective of this study was to compare the effects of anti-RSV-G and anti-RSV-F monoclonal antibodies (mAbs) on airway hyperresponsiveness (AHR) and inflammation after primary or secondary RSV infection in mice. In the primary infection model, mice were infected with RSV at 6 weeks of age. Anti-RSV-G or anti-RSV-F mAbs were administered 24 hours before infection or Day +2 postinfection. In a secondary infection model, mice were infected (primary) with RSV at 1 week (neonate) and reinfected (secondary) 5 weeks later. Anti-RSV-G and anti-RSV-F mAbs were administered 24 hours before the primary infection. Both mAbs had comparable effects in preventing airway responses after primary RSV infection. When given 2 days after infection, anti-RSV-G-treated mice showed significantly decreased AHR and airway inflammation, which persisted in anti-RSV-F-treated mice. In the reinfection model, anti-RSV-G but not anti-RSV-F administered during primary RSV infection in neonates resulted in decreased AHR, eosinophilia, and IL-13 but increased levels of IFN-γ in bronchoalveolar lavage on reinfection. These results support the use of anti-RSV-G in the prevention and treatment of RSV-induced disease.
呼吸道合胞病毒(RSV)是全球范围内婴儿下呼吸道疾病的主要病因。RSV-G和RSV-F糖蛋白在RSV感染过程中均发挥致病作用。本研究的目的是比较抗RSV-G和抗RSV-F单克隆抗体(mAb)对小鼠初次或二次RSV感染后气道高反应性(AHR)和炎症的影响。在初次感染模型中,6周龄小鼠感染RSV。在感染前24小时或感染后第2天给予抗RSV-G或抗RSV-F mAb。在二次感染模型中,1周龄(新生小鼠)小鼠初次感染RSV,5周后再次感染(二次感染)。在初次感染前24小时给予抗RSV-G和抗RSV-F mAb。两种mAb在预防初次RSV感染后的气道反应方面具有相似的效果。感染后2天给药时,抗RSV-G治疗的小鼠AHR和气道炎症显著降低,而抗RSV-F治疗的小鼠则持续存在。在再感染模型中,新生小鼠初次RSV感染期间给予抗RSV-G而非抗RSV-F,导致再感染时AHR降低、嗜酸性粒细胞增多和IL-13水平降低,但支气管肺泡灌洗中IFN-γ水平升高。这些结果支持抗RSV-G用于预防和治疗RSV诱导的疾病。