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Immune memory shapes human polyclonal antibody responses to H2N2 vaccination

Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural and biochemical...

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Autores principales: Yang, Yuhe R., Han, Julianna, Perrett, Hailee R., Richey, Sara T., Jackson, Abigail M., Rodriguez, Alesandra J., Gillespie, Rebecca A., O’Connell, Sarah, Raab, Julie E., Cominsky, Lauren Y., Chopde, Ankita, Kanekiyo, Masaru, Houser, Katherine V., Chen, Grace L., McDermott, Adrian B., Andrews, Sarah F., Ward, Andrew B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541104/
https://www.ncbi.nlm.nih.gov/pubmed/37781590
http://dx.doi.org/10.1101/2023.08.23.554525
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author Yang, Yuhe R.
Han, Julianna
Perrett, Hailee R.
Richey, Sara T.
Jackson, Abigail M.
Rodriguez, Alesandra J.
Gillespie, Rebecca A.
O’Connell, Sarah
Raab, Julie E.
Cominsky, Lauren Y.
Chopde, Ankita
Kanekiyo, Masaru
Houser, Katherine V.
Chen, Grace L.
McDermott, Adrian B.
Andrews, Sarah F.
Ward, Andrew B.
author_facet Yang, Yuhe R.
Han, Julianna
Perrett, Hailee R.
Richey, Sara T.
Jackson, Abigail M.
Rodriguez, Alesandra J.
Gillespie, Rebecca A.
O’Connell, Sarah
Raab, Julie E.
Cominsky, Lauren Y.
Chopde, Ankita
Kanekiyo, Masaru
Houser, Katherine V.
Chen, Grace L.
McDermott, Adrian B.
Andrews, Sarah F.
Ward, Andrew B.
author_sort Yang, Yuhe R.
collection PubMed
description Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited after H2 vaccination. We temporally map the epitopes targeted by serum antibodies after first and second vaccinations and show previous H2 exposure results in higher responses to the variable head domain of hemagglutinin while initial responses in H2-naïve participants are dominated by antibodies targeting conserved epitopes. We use cryo-EM and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the hemagglutinin head including the receptor binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses.
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spelling pubmed-105411042023-10-01 Immune memory shapes human polyclonal antibody responses to H2N2 vaccination Yang, Yuhe R. Han, Julianna Perrett, Hailee R. Richey, Sara T. Jackson, Abigail M. Rodriguez, Alesandra J. Gillespie, Rebecca A. O’Connell, Sarah Raab, Julie E. Cominsky, Lauren Y. Chopde, Ankita Kanekiyo, Masaru Houser, Katherine V. Chen, Grace L. McDermott, Adrian B. Andrews, Sarah F. Ward, Andrew B. bioRxiv Article Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited after H2 vaccination. We temporally map the epitopes targeted by serum antibodies after first and second vaccinations and show previous H2 exposure results in higher responses to the variable head domain of hemagglutinin while initial responses in H2-naïve participants are dominated by antibodies targeting conserved epitopes. We use cryo-EM and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the hemagglutinin head including the receptor binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses. Cold Spring Harbor Laboratory 2023-08-24 /pmc/articles/PMC10541104/ /pubmed/37781590 http://dx.doi.org/10.1101/2023.08.23.554525 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Yang, Yuhe R.
Han, Julianna
Perrett, Hailee R.
Richey, Sara T.
Jackson, Abigail M.
Rodriguez, Alesandra J.
Gillespie, Rebecca A.
O’Connell, Sarah
Raab, Julie E.
Cominsky, Lauren Y.
Chopde, Ankita
Kanekiyo, Masaru
Houser, Katherine V.
Chen, Grace L.
McDermott, Adrian B.
Andrews, Sarah F.
Ward, Andrew B.
Immune memory shapes human polyclonal antibody responses to H2N2 vaccination
title Immune memory shapes human polyclonal antibody responses to H2N2 vaccination
title_full Immune memory shapes human polyclonal antibody responses to H2N2 vaccination
title_fullStr Immune memory shapes human polyclonal antibody responses to H2N2 vaccination
title_full_unstemmed Immune memory shapes human polyclonal antibody responses to H2N2 vaccination
title_short Immune memory shapes human polyclonal antibody responses to H2N2 vaccination
title_sort immune memory shapes human polyclonal antibody responses to h2n2 vaccination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541104/
https://www.ncbi.nlm.nih.gov/pubmed/37781590
http://dx.doi.org/10.1101/2023.08.23.554525
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