Structure-guided loop grafting improves expression and stability of influenza neuraminidase for vaccine development
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| Title: | Structure-guided loop grafting improves expression and stability of influenza neuraminidase for vaccine development |
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| Authors: | Pramila Rijal, Leiyan Wei, Guido C Paesen, David I Stuart, Mark Haworth, Kuan-Ying A Huang, Thomas A Bowden, Alain RM Townsend |
| Source: | eLife, Vol 14 (2025) |
| Publisher Information: | eLife Sciences Publications Ltd, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | influenza virus, neuraminidase, protein expression, loop grafting, vaccine, Medicine, Science, Biology (General), QH301-705.5 |
| Description: | Influenza virus neuraminidase (NA) is a crucial target for protective antibodies, yet the development of recombinant NA protein as a vaccine has been held back by instability and variable expression. We have taken a pragmatic approach to improving expression and stability of NA by grafting antigenic surface loops from low-expressing NA proteins onto the scaffold of high-expressing counterparts. The resulting hybrid proteins retained the antigenic properties of the loop donor while benefiting from the high-yield expression, stability, and tetrameric structure of the loop recipient. These hybrid proteins were recognised by a broad set of human monoclonal antibodies elicited by influenza infection or vaccination, with X-ray structures validating the accurate structural conformation of the grafted loops and the enzymatic cavity. Immunisation of mice with NA hybrids induced inhibitory antibodies to the loop donor and protected against lethal influenza challenge. This pragmatic technique offers a robust solution for improving the expression and stability of influenza NA proteins for vaccine development. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/105317; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.105317 |
| Access URL: | https://doaj.org/article/ce79935d8e784bcc99bf7da3c5b90fcc |
| Accession Number: | edsdoj.79935d8e784bcc99bf7da3c5b90fcc |
| Database: | Directory of Open Access Journals |
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Nájsť tento článok vo Web of Science | Abstract: | Influenza virus neuraminidase (NA) is a crucial target for protective antibodies, yet the development of recombinant NA protein as a vaccine has been held back by instability and variable expression. We have taken a pragmatic approach to improving expression and stability of NA by grafting antigenic surface loops from low-expressing NA proteins onto the scaffold of high-expressing counterparts. The resulting hybrid proteins retained the antigenic properties of the loop donor while benefiting from the high-yield expression, stability, and tetrameric structure of the loop recipient. These hybrid proteins were recognised by a broad set of human monoclonal antibodies elicited by influenza infection or vaccination, with X-ray structures validating the accurate structural conformation of the grafted loops and the enzymatic cavity. Immunisation of mice with NA hybrids induced inhibitory antibodies to the loop donor and protected against lethal influenza challenge. This pragmatic technique offers a robust solution for improving the expression and stability of influenza NA proteins for vaccine development. |
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| ISSN: | 2050084X |
| DOI: | 10.7554/eLife.105317 |