Background: The 2009 influenza pandemics underscored the need for effective vaccines to block the spread of influenza virus infection. Most live attenuated vaccines utilize cold-adapted, temperature-sensitive virus. An alternative to live attenuated virus is presented here, based on microRNA-induced gene silencing. Methods: In this study, miR-let-7b target sequences were inserted into the H1N1 genome to engineer a recombinant virus - miRT-H1N1. Female BALB/c mice were vaccinated intranasally with the miRT-H1N1 and challenged with a lethal dose of homologous virus. Results: This miRT-H1N1 virus was attenuated in mice, while it exhibited wild-type characteristics in chicken embryos. Mice vaccinated intranasally with the miRT-H1N1 responded with robust immunity that protected the vaccinated mice from a lethal challenge with the wild-type 2009 pandemic H1N1 virus. Conclusions: These results indicate that the influenza virus containing microRNA response elements (MREs) is attenuated in vivo and can be used to design a live attenuated vaccine.
Bibliographical noteFunding Information:
This study was supported in part by the National Science Foundation of China (NSFC 81200063) and by a grant from the Hospital Foundation of Jinling Hospital (No. 2013021).
- Live attenuated vaccine