tetano
Editor, Senior Moderator
ACS Synth Biol. 2019 Sep 30. doi: 10.1021/acssynbio.9b00094. [Epub ahead of print] [h=1]Generation of Stable Influenza Virus Hemagglutinin through Structure-Guided Recombination.[/h]
Tsai CH[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Wei SC[SUP]2,[/SUP][SUP]3[/SUP], Jan JT[SUP]4[/SUP], Liao LL[SUP]2[/SUP], Chang CJ[SUP]2[/SUP], Chao YC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h] 1 Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science , National Defense Medical Center , Taipei 115 , Taiwan, ROC. 2 Institute of Molecular Biology, Academia Sinica , Taipei 115 , Taiwan, ROC. 3 Graduate Institute of Life Sciences , National Defense Medical Center , Taipei 114 , Taiwan, ROC. 4 Genomics Research Center , Academia Sinica , Taipei 115 , Taiwan, ROC. 5 Department of Plant Pathology and Microbiology, College of Bioresources and Agriculture , National Taiwan University , Taipei 106 , Taiwan, ROC. 6 Department of Life Sciences, College of Life Sciences , National Chung Hsing University , Taichung 402 , Taiwan, ROC. 7 Department of Entomology, College of Agriculture and Natural Resources , National Chung Hsing University , Taichung 402 , Taiwan, ROC.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] SCHEMA; baculovirus; hemagglutinin; influenza virus; structure-guided recombination; thermal stability
PMID: 31565926 DOI: 10.1021/acssynbio.9b00094
Tsai CH[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Wei SC[SUP]2,[/SUP][SUP]3[/SUP], Jan JT[SUP]4[/SUP], Liao LL[SUP]2[/SUP], Chang CJ[SUP]2[/SUP], Chao YC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h] 1 Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science , National Defense Medical Center , Taipei 115 , Taiwan, ROC. 2 Institute of Molecular Biology, Academia Sinica , Taipei 115 , Taiwan, ROC. 3 Graduate Institute of Life Sciences , National Defense Medical Center , Taipei 114 , Taiwan, ROC. 4 Genomics Research Center , Academia Sinica , Taipei 115 , Taiwan, ROC. 5 Department of Plant Pathology and Microbiology, College of Bioresources and Agriculture , National Taiwan University , Taipei 106 , Taiwan, ROC. 6 Department of Life Sciences, College of Life Sciences , National Chung Hsing University , Taichung 402 , Taiwan, ROC. 7 Department of Entomology, College of Agriculture and Natural Resources , National Chung Hsing University , Taichung 402 , Taiwan, ROC.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] SCHEMA; baculovirus; hemagglutinin; influenza virus; structure-guided recombination; thermal stability
PMID: 31565926 DOI: 10.1021/acssynbio.9b00094