Recombinant live attenuated influenza vaccine viruses carrying CD8 T-cell epitopes of respiratory syncytial virus protect mice against both pathogens without inflammatory disease

Abstract

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.