Graham B S, Henderson G S, Tang Y W, Lu X, Neuzil K M, Colley D G
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
J Immunol. 1993 Aug 15;151(4):2032-40.
Defining the mechanism for the vaccine-enhanced illness associated with respiratory syncytial virus (RSV) is critical for advancing RSV vaccine development. Previous studies in which infants were vaccinated with formalin-inactivated alum-precipitated whole virus did not protect from RSV infection, and those infected had a high incidence of severe illness. In contrast, previous clinical trials evaluating live attenuated RSV showed no associated vaccine-enhanced illness. We have used a mouse model to explore the immunopathogenesis of RSV infection. In this study cytokine mRNA expression was examined using 32P-labeled oligonucleotide probes in Northern blot analyses of polyA RNA extracted from lungs of mice primed with various vaccine preparations then challenged nasally with live RSV. We have shown that upon challenge, priming of mice with inactivated virus or subunit F glycoprotein induced a pattern of cytokine mRNA expression suggesting a dominant Th2-like lymphocyte response (relative increase in IL-4 mRNA expression). In contrast, challenge of mice primed with live RSV by parenteral or mucosal routes induced a Th1-like pattern of cytokine mRNA expression (relative decrease in IL-4 mRNA expression compared to IFN-gamma mRNA expression). Thus, the formulation and route of delivery of vaccine products can influence the pattern of cytokine expression in lung upon RSV challenge.
明确与呼吸道合胞病毒（RSV）相关的疫苗增强疾病的机制对于推进RSV疫苗的研发至关重要。此前对婴儿接种福尔马林灭活的明矾沉淀全病毒疫苗的研究未能预防RSV感染，且感染的婴儿患重症的发生率很高。相比之下，此前评估减毒活RSV的临床试验未显示出相关的疫苗增强疾病。我们使用小鼠模型来探究RSV感染的免疫发病机制。在本研究中，利用32P标记的寡核苷酸探针，通过Northern印迹分析，检测用各种疫苗制剂预处理后经鼻腔接种活RSV的小鼠肺中提取的多聚腺苷酸RNA中的细胞因子mRNA表达。我们已经表明，在受到攻击时，用灭活病毒或亚单位F糖蛋白预处理小鼠会诱导细胞因子mRNA表达模式，提示主要为Th2样淋巴细胞反应（IL-4 mRNA表达相对增加）。相比之下，经肠胃外或粘膜途径用活RSV预处理的小鼠受到攻击时会诱导Th1样细胞因子mRNA表达模式（与IFN-γ mRNA表达相比，IL-4 mRNA表达相对降低）。因此，疫苗产品的配方和给药途径可影响RSV攻击时肺中细胞因子的表达模式。
