tetano
Editor, Senior Moderator
JCI Insight
. 2023 Jun 8;e167464.
doi: 10.1172/jci.insight.167464. Online ahead of print. Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
Hillary A Vanderven[SUP] 1 [/SUP], Deborah N Wentworth[SUP] 2 [/SUP], Win Min Han[SUP] 3 [/SUP], Heidi Peck[SUP] 4 [/SUP], Ian G Barr[SUP] 5 [/SUP], Richard T Davey Jr[SUP] 6 [/SUP], John H Beigel[SUP] 7 [/SUP], Dominic E Dwyer[SUP] 8 [/SUP], Mamta K Jain[SUP] 9 [/SUP], Brian Angus[SUP] 10 [/SUP], Christian T Brandt[SUP] 11 [/SUP], Analia Mykietiuk[SUP] 12 [/SUP], Matthew G Law[SUP] 3 [/SUP], James D Neaton[SUP] 13 [/SUP], Stephen J Kent[SUP] 14 [/SUP]
Affiliations
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.
Clinicaltrials: gov NCT02287467FUNDING SOURCES. Funding for this research was provided by Subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.
Keywords: Adaptive immunity; Immunology; Infectious disease; Influenza; NK cells.
. 2023 Jun 8;e167464.
doi: 10.1172/jci.insight.167464. Online ahead of print. Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza
Hillary A Vanderven[SUP] 1 [/SUP], Deborah N Wentworth[SUP] 2 [/SUP], Win Min Han[SUP] 3 [/SUP], Heidi Peck[SUP] 4 [/SUP], Ian G Barr[SUP] 5 [/SUP], Richard T Davey Jr[SUP] 6 [/SUP], John H Beigel[SUP] 7 [/SUP], Dominic E Dwyer[SUP] 8 [/SUP], Mamta K Jain[SUP] 9 [/SUP], Brian Angus[SUP] 10 [/SUP], Christian T Brandt[SUP] 11 [/SUP], Analia Mykietiuk[SUP] 12 [/SUP], Matthew G Law[SUP] 3 [/SUP], James D Neaton[SUP] 13 [/SUP], Stephen J Kent[SUP] 14 [/SUP]
Affiliations
- PMID: 37289541
- DOI: 10.1172/jci.insight.167464
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.
Clinicaltrials: gov NCT02287467FUNDING SOURCES. Funding for this research was provided by Subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.
Keywords: Adaptive immunity; Immunology; Infectious disease; Influenza; NK cells.