Vanderven, Hillary A., Wragg, Kathleen, Ana-Sosa-Batiz, Fernanda, Kristensen, Anne B., Jegaskanda, Sinthujan, Wheatley, Adam K., Wentworth, Deborah, Wines, Bruce D., Hogarth, P. Mark, Rockman, Steve, Kent, Stephen J., and INSIGHT FLU005 Pilot Study Writing Group (2018) Anti-influenza hyperimmune immunoglobulin enhances Fc-functional antibody immunity during human influenza infection. Journal of Infectious Diseases, 218 (9). pp. 1383-1393.

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Abstract

Background: New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralizing antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear.

Methods: We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fcγ receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study.

Results: Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1–3 days against infecting and noninfecting strains of influenza.

Conclusions: Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus, and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralizing antibodies in the Flu-IVIG preparation.

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