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Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza

BACKGROUND: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B bu...

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Autores principales: Vanderven, Hillary A., Wentworth, Deborah N., Han, Win Min, Peck, Heidi, Barr, Ian G., Davey, Richard T., Beigel, John H., Dwyer, Dominic E., Jain, Mamta K., Angus, Brian, Brandt, Christian T., Mykietiuk, Analia, Law, Matthew G., Neaton, James D., Kent, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443807/
https://www.ncbi.nlm.nih.gov/pubmed/37289541
http://dx.doi.org/10.1172/jci.insight.167464
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author Vanderven, Hillary A.
Wentworth, Deborah N.
Han, Win Min
Peck, Heidi
Barr, Ian G.
Davey, Richard T.
Beigel, John H.
Dwyer, Dominic E.
Jain, Mamta K.
Angus, Brian
Brandt, Christian T.
Mykietiuk, Analia
Law, Matthew G.
Neaton, James D.
Kent, Stephen J.
author_facet Vanderven, Hillary A.
Wentworth, Deborah N.
Han, Win Min
Peck, Heidi
Barr, Ian G.
Davey, Richard T.
Beigel, John H.
Dwyer, Dominic E.
Jain, Mamta K.
Angus, Brian
Brandt, Christian T.
Mykietiuk, Analia
Law, Matthew G.
Neaton, James D.
Kent, Stephen J.
author_sort Vanderven, Hillary A.
collection PubMed
description BACKGROUND: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A. METHODS: To probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays. RESULTS: Influenza-specific FcγR-binding antibodies were elevated in Flu-IVIG–infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody. CONCLUSION: These detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02287467. FUNDING: Funding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.
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spelling pubmed-104438072023-08-23 Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza Vanderven, Hillary A. Wentworth, Deborah N. Han, Win Min Peck, Heidi Barr, Ian G. Davey, Richard T. Beigel, John H. Dwyer, Dominic E. Jain, Mamta K. Angus, Brian Brandt, Christian T. Mykietiuk, Analia Law, Matthew G. Neaton, James D. Kent, Stephen J. JCI Insight Clinical Medicine BACKGROUND: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A. METHODS: To probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays. RESULTS: Influenza-specific FcγR-binding antibodies were elevated in Flu-IVIG–infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody. CONCLUSION: These detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02287467. FUNDING: Funding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID. American Society for Clinical Investigation 2023-07-24 /pmc/articles/PMC10443807/ /pubmed/37289541 http://dx.doi.org/10.1172/jci.insight.167464 Text en © 2023 Vanderven et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical Medicine
Vanderven, Hillary A.
Wentworth, Deborah N.
Han, Win Min
Peck, Heidi
Barr, Ian G.
Davey, Richard T.
Beigel, John H.
Dwyer, Dominic E.
Jain, Mamta K.
Angus, Brian
Brandt, Christian T.
Mykietiuk, Analia
Law, Matthew G.
Neaton, James D.
Kent, Stephen J.
Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
title Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
title_full Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
title_fullStr Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
title_full_unstemmed Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
title_short Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
title_sort understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (flu-ivig) for severe human influenza
topic Clinical Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443807/
https://www.ncbi.nlm.nih.gov/pubmed/37289541
http://dx.doi.org/10.1172/jci.insight.167464
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