Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2018-01, Vol.359 (6373), p.290-296

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2018

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.