Both immunisation with a formalin-inactivated respiratory syncytial virus (RSV) vaccine and a mock antigen vaccine induce severe lung pathology and a Th2 cytokine profile in RSV-challenged mice
Both immunisation with a formalin-inactivated respiratory syncytial virus (RSV) vaccine and a mock antigen vaccine induce severe lung pathology and a Th2 cytokine profile in RSV-challenged mice
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DOI：
10.1016/s0264-410x(00)00213-9
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发表时间：
2000-11-22
期刊：
影响因子：
5.5
通讯作者：
Kimman, T
中科院分区：
文献类型：
--
作者：
Boelen, A;Andeweg, A;Kimman, T
呼吸道合胞病毒（RSV）是婴幼儿毛细支气管炎和肺炎的最重要原因。免疫病理学可能在RSV诱导的疾病中发挥作用，严重的RSV感染也可能与哮喘发生风险增加相关。在感染前用福尔马林灭活的RSV（FI-RSV）接种导致人和小鼠模型中广泛的肺部病理学。在小鼠模型中，已经表明这种疾病的加重与Th 1和Th 2细胞因子之间的平衡向Th 2型应答的转变有关。本研究的目的是观察BALB/c小鼠在RSV感染后的免疫和炎症反应，无论是否预先接种铝佐剂FI-RSV或对照抗原（FI-Mock）。正如其他人先前报道的那样，我们还观察到BALB/c小鼠中的原发性RSV感染导致主要的Th 1型细胞因子应答，这与轻微的细支气管炎和肺泡炎相关。在RSV攻击前接种FI-RSV疫苗可防止病毒复制，并与肺组织病理学恶化和向Th 2型应答转变相关。用FI-Mock接种疫苗不能阻止RSV在肺中的复制，但在感染后导致甚至更明显的Th 2应答，而这些小鼠对特异性病毒抗原不敏感。因此，Th 2应答动物中的病毒复制（由铝佐剂模拟疫苗诱导）似乎增强RSV感染后的Th 2应答。(C)2000爱思唯尔科技有限公司版权所有。
Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children. Immunopathology may play a role in RSV-induced disease and a severe RSV infection may also be associated with an increased risk of developing asthma. Vaccination with formalin-inactivated RSV (FI-RSV) prior to infection resulted both in human and in the mouse model in extensive lung pathology. In the mouse model, it has been shown that this aggravation of disease was associated with a shift in the balance between Th1 and Th2 cytokines towards a Th2-type response. The aim of the present study was to characterise the immunological and inflammatory responses in BALB/c mice upon RSV infection with or without prior vaccination with aluminium-adjuvanted FI-RSV or control antigens (FI-Mock). As previously reported by others, we also observed that a primary RSV infection in BALB/c mice resulted in a predominant Th1-type cytokine response, which was associated with slight bronchiolitis and alveolitis. FI-RSV vaccination prior to RSV challenge prevented virus replication and was associated with an aggravation of pulmonary histopathology and a shift towards a Th2-type response. Vaccination with FI-Mock did not prevent RSV replication in the lung but resulted in an even more pronounced Th2 response after infection while these mice were not sensitised to specific viral antigens. Thus, viral replication in a Th2 responding animal (induced by aluminium-adjuvanted mock vaccine) appears to boost the Th2 response upon RSV infection. (C) 2000 Elsevier Science Ltd. All rights reserved.