Generation of Stable Influenza Virus Hemagglutinin through Structure-Guided Recombination

Chih Hsuan Tsai, Sung Chan Wei, Jia Tsrong Jan, Lin Li Liao, Chia Jung Chang, Yu Chan Chao

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

Hemagglutinin (HA) is the major surface antigen of influenza virus and the most promising influenza vaccine immunogen. In 2013, the devastating H7N9 influenza virus was identified in China, which induced high mortality. The HA of this virus (H7) is relatively unstable, making it challenging to produce an effective vaccine. To improve the stability of HA protein from H7N9 influenza virus for better vaccine antigens without impairing immunogenicity, we recombined the HA from H7N9 (H7) with a more stable HA from H3N2 (H3) by structure-guided recombination, resulting in six chimeric HAs, FrA-FrF. Two of these chimeric HAs, FrB and FrC, exhibited proper hemagglutination activity and presented improved thermal stability compared to the original H7. Mice immunized with FrB and FrC elicited H7-specific antibodies comparable to those induced by parental H7, and the antisera collected from these immunized mice successfully inhibited H7N9 infection in a microneutralization assay. These results suggest that our structural-recombination approach can create stabilizing chimeric antigens while maintaining proper immunogenicity, which may not only benefit the construction of more stable HA vaccines to fight against H7N9 infection, but also facilitate effective vaccine improvements for other influenza viruses or infectious pathogens. In addition, this study also demonstrates the potential for better engineering of multimeric protein complexes like HA to achieve improved function, which are often immunologically or pharmaceutically important but difficult to modify.

原文English
頁(從 - 到)2472-2482
頁數11
期刊ACS Synthetic Biology
8
發行號11
DOIs
出版狀態Published - 2019 11月 15

All Science Journal Classification (ASJC) codes

  • 生物醫學工程
  • 生物化學、遺傳與分子生物學(雜項)

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