Effect and mechanism of defective interfering particles (DIPs) in live attenuated influenza vaccine on attenuated and immune activation

Defective interfering particles (DIPs) are defective viral genome (DVG)-containing particles which are generated in virus replication. Our studies indicated that DIP interferes the replication and encapsidation of standard virus (STV). DIPs are found in various sorts of live attenuated vaccines, they may contribute to virulence attenuation. DIPs also showed potential of activation of innate immune response (IFN synthesis), which may be essential for the vaccine immunogenicity. However, systematic researches on DIPs are lacking. The influenza is a severe public health threat, and the protection rate of influenza vaccines is always unstable. At the time when the first LAIV in China was approved for marketing this year, it is urgent to trigger deep studies focusing DIPs within it. In the preliminary experiments of this project, DVGs in the LAIV were sequenced. We will study interfering mechanisms of DIPs which contain different single defective segment against STV replication, the mechanisms how DIPs elicit immune response, and the heterogenic features inside using single-cell sequencing approach. Based on these knowledges, the contribution of DIPs to virulence attenuation of LAIV will be researched. Furthermore, the proper DIP concentration range for optimized effects of LAIV on both attenuation and immunogenicity will be identified. As the importance, this project will provide theoretical basis for efficacy optimization and establishment of quality control standard of LAIV, and is also valuable for related concerns in LAIV vectored vaccine design like COVID-19 and HIV vaccines as well as in studies of other live attenuated virus vaccines.