Vanderven, Hillary, 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., and Kent, Stephen J. (2023) Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza. JCI Insight, 8 (14). e167464.

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Abstract

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.

Item ID:	79386
Item Type:	Article (Research - C1)
ISSN:	2379-3708
Copyright Information:	© 2023, Vanderven et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Date Deposited:	15 Aug 2023 22:54
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 75% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 25%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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