Anti-influenza hyperimmune immunoglobulin enhances Fc-functional antibody immunity during human influenza infection

Journal Publication ResearchOnline@JCU
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.;INSIGHT FLU005 Pilot Study Writing Group,
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.

Journal

Journal of Infectious Diseases

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Volume

218

ISBN/ISSN

1537-6613

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Issue

9

Pages Count

11

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Publisher

University of Chicago Press

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DOI

10.1093/infdis/jiy328