Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tiziano Gaiotto, Walter Ramage, Christina Ball, Paul Risley, George W. Carnell, Nigel Temperton, Othmar G. Engelhardt, Simon E. Hufton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/204a4bf957ea4639994ee314f4ba3f3d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:204a4bf957ea4639994ee314f4ba3f3d
record_format	dspace
spelling	oai:doaj.org-article:204a4bf957ea4639994ee314f4ba3f3d2021-12-02T10:44:15ZNanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display10.1038/s41598-021-82356-42045-2322https://doaj.org/article/204a4bf957ea4639994ee314f4ba3f3d2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82356-4https://doaj.org/toc/2045-2322Abstract 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.Tiziano GaiottoWalter RamageChristina BallPaul RisleyGeorge W. CarnellNigel TempertonOthmar G. EngelhardtSimon E. HuftonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiziano Gaiotto Walter Ramage Christina Ball Paul Risley George W. Carnell Nigel Temperton Othmar G. Engelhardt Simon E. Hufton Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
description	Abstract 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.
format	article
author	Tiziano Gaiotto Walter Ramage Christina Ball Paul Risley George W. Carnell Nigel Temperton Othmar G. Engelhardt Simon E. Hufton
author_facet	Tiziano Gaiotto Walter Ramage Christina Ball Paul Risley George W. Carnell Nigel Temperton Othmar G. Engelhardt Simon E. Hufton
author_sort	Tiziano Gaiotto
title	Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
title_short	Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
title_full	Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
title_fullStr	Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
title_full_unstemmed	Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display
title_sort	nanobodies mapped to cross-reactive and divergent epitopes on a(h7n9) influenza hemagglutinin using yeast display
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/204a4bf957ea4639994ee314f4ba3f3d
work_keys_str_mv	AT tizianogaiotto nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT walterramage nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT christinaball nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT paulrisley nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT georgewcarnell nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT nigeltemperton nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT othmargengelhardt nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay AT simonehufton nanobodiesmappedtocrossreactiveanddivergentepitopesonah7n9influenzahemagglutininusingyeastdisplay
_version_	1718396752256565248

Nanobodies mapped to cross-reactive and divergent epitopes on A(H7N9) influenza hemagglutinin using yeast display

Ejemplares similares