Contribution of respiratory syncytial virus G antigenicity to vaccine-enhanced illness and the implications for severe disease during primary respiratory syncytial virus infection
Contribution of respiratory syncytial virus G antigenicity to vaccine-enhanced illness and the implications for severe disease during primary respiratory syncytial virus infection
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DOI：
10.1097/01.inf.0000108192.94692.d2
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发表时间：
2004-01-01
影响因子：
3.6
通讯作者：
Graham, BS
中科院分区：
文献类型：
--
作者：
Johnson, TR;Graham, BS
背景用表达呼吸道合胞病毒（RSV）的G糖蛋白（vvG）的牛痘病毒或用福尔马林灭活的明矾沉淀的RSV（FI-RSV）免疫BALB/c小鼠在用活RSV攻击后易患严重疾病、产生2型细胞因子和肺嗜酸性粒细胞增多症。这种相似的疾病特征导致了以下建议：FI-RSV制剂中G糖蛋白的存在是20世纪60年代失败的临床试验中观察到的疫苗相关疾病增强的免疫学基础。然而，在FI-RSV-和vvG-免疫的小鼠中观察到的疾病发病机理的过程表明，FI-RSV和vG免疫诱导不同组成和要求的免疫应答，其在活病毒攻击后会聚以产生相似的疾病结果。在小鼠中探索了FI-RSV制剂中存在的RSV G在增加免疫后疾病严重程度中的潜在作用。在FI-RSV免疫期间不存在RSV G或其免疫显性表位不会降低RSV攻击后的疾病严重程度。此外，尽管RSV攻击期间V β 14（+）T细胞的耗竭调节了G致敏小鼠的疾病，但对FI-RSV免疫小鼠的疾病影响最小。FI-RSV疫苗增强的疾病不能归因于RSV G。此外，安全有效的RSV疫苗的配制必须确保RSV抗原通过内源性途径产生、加工和呈递。因此，通过载体、通过DNA或通过活减毒病毒的基因递送是有吸引力的疫苗方法。
Background. Immunization of BALB/c mice with vaccinia virus expressing the G glycoprotein (vvG) of respiratory syncytial virus (RSV) or with formalin-inactivated alum-precipitated RSV (FI-RSV) predisposes for severe illness, type 2 cytokine production and pulmonary eosinophilia after challenge with live RSV. This similar disease profile has led to the proposal that the presence of the G glycoprotein in the FI-RSV preparation was the immunologic basis for the vaccine-associated enhancement of disease observed in the failed clinical trials of the 1960s. However, processes of disease pathogenesis observed in FI-RSV- and vvG-immunized mice suggest that FI-RSV and vvG immunizations induce immune responses of different compositions and requirements that converge to produce similar disease outcomes upon live virus challenge.Methods. The potential role of RSV G present in FI-RSV preparations in increasing postimmunization disease severity was explored in mice.Results. The absence of RSV G or its immunodominant epitope during FI-RSV immunization does not reduce disease severity after RSV challenge. Furthermore although depletion of Vbeta14(+) T cells during RSV challenge modulates disease in G-primed mice, minimal impact on disease in FI-RSV-immunized mice is observed.Conclusion. FI-RSV vaccine-enhanced illness is not attributable to RSV G. Furthermore formulation of a safe and effective RSV vaccine must ensure RSV antigen production, processing and presentation via the endogenous pathways. Thus gene delivery by vector, by DNA or by live attenuated virus are attractive vaccine approaches.