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

HA Vanderven, K Wragg… - The Journal of …, 2018 - academic.oup.com
HA Vanderven, K Wragg, F Ana-Sosa-Batiz, AB Kristensen, S Jegaskanda, AK Wheatley
The Journal of Infectious Diseases, 2018academic.oup.com
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 …
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.
Oxford University Press