TY - JOUR
T1 - Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
AU - The INSIGHT FLU-IVIG Study Group
AU - Vanderven, Hillary A.
AU - Wentworth, Deborah N.
AU - Han, Win Min
AU - Peck, Heidi
AU - Barr, Ian
AU - Davey, Richard T.
AU - Beigel, John
AU - Dwyer, Dominic
AU - Jain, Mamta
AU - Angus, Brian
AU - Brandt, Christian
AU - Mykietiuk, Analia
AU - Law, Matthew G.
AU - Neaton, Jim D.
AU - Kent, Stephen J.
N1 - Publisher Copyright:
© 2023 American Society for Clinical Investigation. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Background: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalised 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 hospitalised with influenza A or B viruses (IAV or IBV) were analysed for antibody isotype/subclass and Fc-gamma receptor (FcgR) binding by ELISA, bead-based multiplex and NK cell activation assays. Results: Influenza-specific FcgR binding antibodies were elevated in Flu-IVIG infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcgR binding were associated with more favourable outcomes. Flu-IVIG therapy also improved the odds of a more favourable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcgR binding antibody was associated with less favourable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favourable 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.
AB - Background: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalised 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 hospitalised with influenza A or B viruses (IAV or IBV) were analysed for antibody isotype/subclass and Fc-gamma receptor (FcgR) binding by ELISA, bead-based multiplex and NK cell activation assays. Results: Influenza-specific FcgR binding antibodies were elevated in Flu-IVIG infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcgR binding were associated with more favourable outcomes. Flu-IVIG therapy also improved the odds of a more favourable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcgR binding antibody was associated with less favourable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favourable 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.
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U2 - 10.1172/jci.insight.167464
DO - 10.1172/jci.insight.167464
M3 - Article
C2 - 37289541
AN - SCOPUS:85162900796
SN - 2379-3708
JO - JCI Insight
JF - JCI Insight
ER -