Instituto Milenio en Inmunología e Inmunoterapia, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile;
J Immunol. 2014 Jan 1;192(1):214-23. doi: 10.4049/jimmunol.1300118. Epub 2013 Dec 6.
Along with the human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, owing to an inefficient immunological memory, hMPV infection provides limited immune protection against reinfection. Furthermore, hMPV can induce an inadequate Th2 type immune response that causes severe lung inflammation, leading to airway obstruction. Similar to hRSV, it is likely that an effective clearance of hMPV would require a balanced Th1 type immunity by the host, involving the activation of IFN-γ-secreting T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which has been used in newborns for many decades and in several countries as a tuberculosis vaccine. We have previously shown that immunization with BCG strains expressing hRSV Ags can induce an efficient immune response that protects against this virus. In this study, we show that immunization with rBCG strains expressing the phosphoprotein from hMPV also can induce protective Th1 immunity. Mice immunized with rBCG were protected against weight loss, airway inflammation, and viral replication in the lungs after hMPV infection. Our rBCG vaccine also induced the activation of hMPV-specific T cells producing IFN-γ and IL-2, which could protect from hMPV infection when transferred to recipient mice. These data strongly support the notion that rBCG induces protective Th1 immunity and could be considered as an efficient vaccine against hMPV.
除了人类呼吸道合胞病毒（hRSV），人类偏肺病毒（hMPV）也是导致儿童住院和全球重大健康负担的主要原因之一。不幸的是，由于免疫记忆效率低下，hMPV 感染对再次感染提供的免疫保护有限。此外，hMPV 可诱导不足的 Th2 型免疫反应，导致严重的肺部炎症，导致气道阻塞。与 hRSV 相似，hMPV 的有效清除可能需要宿主产生平衡的 Th1 型免疫，涉及 IFN-γ 分泌 T 细胞的激活。牛分枝杆菌卡介苗（BCG）是公认的 Th1 免疫诱导剂，已在新生儿中使用数十年，并在多个国家作为结核病疫苗使用。我们之前的研究表明，用表达 hRSV 抗原的 BCG 菌株免疫可诱导有效的免疫反应，从而预防这种病毒。在这项研究中，我们表明，用表达 hMPV 磷蛋白的 rBCG 菌株免疫也可以诱导保护性 Th1 免疫。用 rBCG 免疫的小鼠在 hMPV 感染后可防止体重减轻、气道炎症和肺部病毒复制。我们的 rBCG 疫苗还诱导产生 IFN-γ和 IL-2 的 hMPV 特异性 T 细胞激活，当转移到受体小鼠中时，可预防 hMPV 感染。这些数据有力地支持了 rBCG 诱导保护性 Th1 免疫的观点，并可被视为针对 hMPV 的有效疫苗。
