Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication




Journal article


JCI Insight

Publication Date



Adaptive immunity, Immunology, Infectious disease, Influenza, NK cells