Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
| Autor: | Paul Risley, Tiziano Gaiotto, Walter Ramage, Simon E. Hufton, Christina Ball, Nigel J. Temperton, George Carnell, Othmar G. Engelhardt |
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| Přispěvatelé: | Apollo - University of Cambridge Repository, Carnell, George [0000-0001-8875-0989] |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Lineage (genetic) Molecular biology Protein Conformation Science Immunology Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Saccharomyces cerevisiae Yeast display Biology Antibodies Viral Influenza A Virus H7N9 Subtype Virus Neutralization Epitope Birds Epitopes Peptide Library Influenza Human Animals Humans Protein Interaction Domains and Motifs Amino Acid Sequence QR355 Multidisciplinary 631/1647 Binding Sites Drug discovery 631/250 Biological techniques 631/154 article food and beverages Single-Domain Antibodies Virology Antibodies Neutralizing Natural sequence Influenza in Birds biology.protein Medicine Antibody 631/61 631/337 Biotechnology Protein Binding |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
| Popis: | Influenza H7N9 virus continues to cause infections in humans and represents a significant pandemic risk. During the most recent 5th epidemic wave in 2016/17 two distinct lineages with increased human infections and wider geographical spread emerged. In preparation for any future adaptations, broadly reactive antibodies against H7N9 are required for surveillance, therapy and prophylaxis. In this study we have isolated a panel of nanobodies (Nbs) with broad reactivity across H7 influenza strains, including H7N9 strains between 2013 and 2017. We also describe Nbs capable of distinguishing between the most recent high and low pathogenicity Yangtze River Delta lineage H7N9 strains. Nanobodies were classified into 5 distinct groups based on their epitope footprint determined using yeast display and mutational scanning. The epitope footprint of Nbs capable of distinguishing high pathogenic (HP) A/Guangdong/17SF003/2016 from low pathogenic (LP) A/Hong Kong/125/2017 (H7N9) were correlated to natural sequence divergence in the head domain at lysine 164. Several Nbs binding to the head domain were capable of viral neutralisation. The potency of one nanobody NB7-14 could be increased over 1000-fold to 113 pM by linking two Nbs together. Nbs specific for distinct epitopes on H7N9 may be useful for surveillance or therapy in human or veterinary settings. |
| Databáze: | OpenAIRE |
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