Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the inactivated virus
Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the inactivated virus
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DOI：
10.1099/vir.0.83250-0
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发表时间：
2007-12-01
影响因子：
3.8
通讯作者：
Boivin, Guy
中科院分区：
文献类型：
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作者：
Hamelin, Marie-Eve;Couture, Christian;Boivin, Guy
人类偏肺病毒（hMPV）是一种副粘病毒，可引起人类急性呼吸道感染。表征了用灭活 hMPV 免疫的 BALB/c 小鼠对 hMPV 感染的组织病理学和免疫学反应。用PBS、未感染的LLC-MK2细胞和热灭活的甲型流感病毒或hMPV感染的细胞的上清液（全部在不完全弗氏佐剂中）或热灭活的hMPV（不含佐剂）对动物进行腹膜内免疫，然后用10（8）TCID50病毒鼻内感染。感染后，收集肺样本和支气管肺泡灌洗液，用于测定病毒滴度和细胞因子水平以及进行组织病理学研究。在第 1 天，用灭活 hMPV 和佐剂免疫的小鼠有 26% 死亡，而其他组则没有死亡。单独用 hMPV 或与佐剂免疫的小鼠的支气管肺泡灌洗液中，与嗜酸性粒细胞浸润相关的肺部炎症更明显，并且白细胞介素 4 (IL-4) 和 IL-5 水平升高。与对照组相比，最后两组小鼠的肺部病毒滴度下降了 4-5 log(10)。我们的数据证明了在该动物模型中使用灭活 hMPV 进行免疫相关的风险，并且在开发 hMPV 疫苗时应考虑这种异常反应。
Human metapneumovirus (hMPV) is a paramyxovirus that causes acute respiratory-tract infections in humans. The histopathological and immunological responses to hMPV infection in BALB/c mice immunized with inactivated hMPV were characterized. Animals were immunized intraperitoneally with PBS, supernatant from non-infected LLC-MK2 cells and from heat-inactivated influenza A- or hMPV-infected cells, all in incomplete Freund's adjuvant, or with heat-inactivated hMPV without adjuvant, and then infected intranasally with 10(8) TCID50 virus. Following infection, lung samples and bronchoalveolar lavages were collected for determination of viral titre and cytokine levels and for histopathological studies. On day 1, 26 % of mice immunized with inactivated hMPV and adjuvant died, compared with none in the other groups, There was more significant lung inflammation associated with eosinophilic infiltration, as well as increased levels of interleukin-4 (IL-4) and IL-5, in the bronchoalveolar lavages of mice immunized with hMPV alone or with the adjuvant. Mice from the last two groups had a 4-5 log(10) decrease in their pulmonary viral titres compared with controls. Our data demonstrate the risks associated with immunization using inactivated hMPV in this animal model and that this aberrant response should be considered in the development of hMPV vaccines.