Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design

Yushen Du, Li Xin, Yuan Shi, Tian Hao Zhang, Nicholas C. Wu, Lei Dai, Danyang Gong, Gurpreet Brar, Sara Shu, Jiadi Luo, William Reiley, Yen Wen Tseng, Hongyan Bai, Ting Ting Wu, Jieru Wang, Yuelong Shu, Ren Sun

Research output: Contribution to journalArticle

Abstract

In conventional attenuated viral vaccines, immunogenicity is often suboptimal. Here we present a systematic approach for vaccine development that eliminates interferon (IFN)-modulating functions genome-wide while maintaining virus replication fitness.We applied a quantitative high-Throughput genomics system to influenza A virus that simultaneously measured the replication fitness and IFN sensitivity of mutations across the entire genome. By incorporating eight IFN-sensitive mutations, we generated a hyper-interferon-sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce transient IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges. Our approach, which attenuates the virus and promotes immune responses concurrently, is broadly applicable for vaccine development against other pathogens.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalScience
Volume359
Issue number6373
DOIs
StatePublished - Jan 19 2018
Externally publishedYes

ASJC Scopus subject areas

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    Du, Y., Xin, L., Shi, Y., Zhang, T. H., Wu, N. C., Dai, L., Gong, D., Brar, G., Shu, S., Luo, J., Reiley, W., Tseng, Y. W., Bai, H., Wu, T. T., Wang, J., Shu, Y., & Sun, R. (2018). Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design. Science, 359(6373), 290-296. https://doi.org/10.1126/science.aan8806