Recombinant live attenuated influenza vaccine viruses carrying CD8 T-cell epitopes of respiratory syncytial virus protect mice against both pathogens without inflammatory disease
Recombinant live attenuated influenza vaccine viruses carrying CD8 T-cell epitopes of respiratory syncytial virus protect mice against both pathogens without inflammatory disease
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DOI：
10.1016/j.antivira.2019.05.001
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发表时间：
2019-08-01
影响因子：
7.6
通讯作者：
Rudenko, Larisa
中科院分区：
文献类型：
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作者：
Kotomina, Tatiana;Isakova-Sivak, Irina;Rudenko, Larisa
呼吸道合胞病毒（RSV）是幼儿、老年人和免疫功能低下成人下呼吸道疾病的最常见原因。尽管几十年来开发有效和安全的RSV疫苗一直是高度优先事项，但没有针对RSV的许可疫苗。在各种疫苗平台中，基于许可的冷适应减毒活流感疫苗（LAIV）的病毒载体RSV疫苗可能提供在呼吸道病原体的感染部位诱导足够的粘膜CD 8 T细胞免疫的优势。我们构建了两种表达RSV M2-1蛋白免疫显性T细胞表位的重组LAIV病毒。本研究的结果提供了证据，证明LAIV病毒载体递送的RSV CD 8 T细胞表位可以在小鼠中赋予针对RSV感染的保护作用，而不会引起肺嗜酸性粒细胞增多症和炎性RSV疾病。此外，这些嵌合LAIV-RSV疫苗保留了其减毒表型和保护免受强毒流感病毒的能力，从而提供了使用单一疫苗制剂对抗两种危险的呼吸道病毒病原体的独特方法。
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory disease in young children, elderly and immunocompromised adults. There is no licensed vaccine against RSV although development of an effective and safe RSV vaccine has been a high priority for several decades. Among the various vaccine platforms, the viral-vectored RSV vaccines based on licensed cold-adapted live attenuated influenza vaccine (LAIV) might offer an advantage of inducing adequate mucosal CD8 T cell immunity at the infection site of respiratory pathogens. We constructed two recombinant LAIV viruses expressing immunodominant T-cell epitopes of RSV M2-1 protein. The results in this study provide evidence that RSV CD8 T cell epitopes delivered by LAIV viral vector could confer protection against RSV infection without causing pulmonary eosinophilia and inflammatory RSV disease in mice. In addition, these chimeric LAIV-RSV vaccines retained their attenuated phenotype and ability to protect against virulent influenza virus, thus providing a unique approach to fight against two dangerous respiratory viral pathogens using a single vaccine preparation.