Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it.
Vaccines that elicit broadly cross-neutralizing antibodies, including antibodies that target the conserved stem of hemagglutinin (HA), are being developed as a strategy for next-generation influenza vaccines that protect against influenza across multiple years. However, efficient induction of cross-...
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doaj-7179238de9d04527910581e425d8b71f2021-03-03T20:31:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022243610.1371/journal.pone.0222436Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it.Wei WangRussell VassellHyo Sook SongQiong ChenPaul W KellerSwati VermaEsmeralda Alvarado-FacundoHongquan WanFalko SchmeisserClement A MesedaJerry P WeirCarol D WeissVaccines that elicit broadly cross-neutralizing antibodies, including antibodies that target the conserved stem of hemagglutinin (HA), are being developed as a strategy for next-generation influenza vaccines that protect against influenza across multiple years. However, efficient induction of cross-neutralizing antibodies remains a challenge, and potential escape mutations have not been well characterized. Here we elicited cross-neutralizing antibodies by immunizing animals with the hemagglutinins from H5 and H9 subtype influenza A viruses that are sensitive to neutralization by stem antibodies. We further isolated and characterized an HA stem monoclonal antibody 4C2 that broadly neutralizes group 1 influenza viruses and identified HA mutations that reduced sensitivity to stem antibodies. Our results offer insights for next-generation influenza vaccine strategies for inducing cross-neutralizing antibodies.https://doi.org/10.1371/journal.pone.0222436 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Wang Russell Vassell Hyo Sook Song Qiong Chen Paul W Keller Swati Verma Esmeralda Alvarado-Facundo Hongquan Wan Falko Schmeisser Clement A Meseda Jerry P Weir Carol D Weiss |
spellingShingle |
Wei Wang Russell Vassell Hyo Sook Song Qiong Chen Paul W Keller Swati Verma Esmeralda Alvarado-Facundo Hongquan Wan Falko Schmeisser Clement A Meseda Jerry P Weir Carol D Weiss Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. PLoS ONE |
author_facet |
Wei Wang Russell Vassell Hyo Sook Song Qiong Chen Paul W Keller Swati Verma Esmeralda Alvarado-Facundo Hongquan Wan Falko Schmeisser Clement A Meseda Jerry P Weir Carol D Weiss |
author_sort |
Wei Wang |
title |
Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. |
title_short |
Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. |
title_full |
Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. |
title_fullStr |
Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. |
title_full_unstemmed |
Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. |
title_sort |
generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
Vaccines that elicit broadly cross-neutralizing antibodies, including antibodies that target the conserved stem of hemagglutinin (HA), are being developed as a strategy for next-generation influenza vaccines that protect against influenza across multiple years. However, efficient induction of cross-neutralizing antibodies remains a challenge, and potential escape mutations have not been well characterized. Here we elicited cross-neutralizing antibodies by immunizing animals with the hemagglutinins from H5 and H9 subtype influenza A viruses that are sensitive to neutralization by stem antibodies. We further isolated and characterized an HA stem monoclonal antibody 4C2 that broadly neutralizes group 1 influenza viruses and identified HA mutations that reduced sensitivity to stem antibodies. Our results offer insights for next-generation influenza vaccine strategies for inducing cross-neutralizing antibodies. |
url |
https://doi.org/10.1371/journal.pone.0222436 |
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