Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG
Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG
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DOI：
10.1073/pnas.0806244105
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发表时间：
2008-12-30
影响因子：
11.1
通讯作者：
Kalergis, Alexis M.
中科院分区：
文献类型：
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作者：
Bueno, Susan M.;Gonzalez, Pablo A.;Kalergis, Alexis M.
呼吸道合胞病毒（RSV）是儿童住院的主要原因之一，也是全球主要的健康负担。不幸的是，由于免疫记忆效率低下，RSV感染对再感染提供有限的免疫保护。此外，RSV可诱导不充分的Th 2型免疫应答，导致严重的呼吸道炎症和阻塞。据认为，有效的RSV清除需要诱导平衡的Th 1型免疫，包括IFN-γ分泌细胞毒性T细胞的活化。一种公认的Th 1免疫诱导剂是牛分枝杆菌卡介苗（BCG），几十年来，它已在几个国家作为结核病疫苗用于新生儿。在这里，我们表明，表达RSV抗原的重组卡介苗株免疫小鼠，促进保护性Th 1型抗RSV免疫。用重组BCG免疫后有效地获得产生IFN-γ和IL-2的RSV特异性T细胞的活化。这种类型的T细胞免疫对RSV攻击具有保护作用，并导致气道中炎性细胞浸润的显著减少。此外，用重组BCG免疫的小鼠没有表现出体重减轻和肺病毒载量降低。这些数据强烈支持重组BCG作为针对RSV的有效疫苗，因为其能够促进保护性Th 1免疫。
Respiratory syncytial virus (RSV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, because of an inefficient immunological memory, RSV infection provides limited immune protection against reinfection. Furthermore, RSV can induce an inadequate Th2-type immune response that causes severe respiratory tract inflammation and obstruction. It is thought that effective RSV clearance requires the induction of balanced Th1-type immunity, involving the activation of IFN-gamma-secreting cytotoxic T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guerin (BCG), which has been used in newborns for decades in several countries as a tuberculosis vaccine. Here, we show that immunization with recombinant BCG strains expressing RSV antigens promotes protective Th1-type immunity against RSV in mice. Activation of RSV-specific T cells producing IFN-gamma and IL-2 was efficiently obtained after immunization with recombinant BCG. This type of T cell immunity was protective against RSV challenge and caused a significant reduction of inflammatory cell infiltration in the airways. Furthermore, mice immunized with recombinant BCG showed no weight loss and reduced lung viral loads. These data strongly support recombinant BCG as an efficient vaccine against RSV because of its capacity to promote protective Th1 immunity.