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PLoS One. 2016 Apr 28;11(4):e0154461. doi: 10.1371/journal.pone.0154461. eCollection 2016.

Influenza-Specific Antibody-Dependent Phagocytosis.

Author information

1
Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
2
Drug Delivery, Disposition and Dynamics laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
3
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia.
4
bioCSL Ltd, Parkville, Victoria, Australia.
5
WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
6
Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne, Australia.
7
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia.

Abstract

BACKGROUND:

Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized.

METHODS:

We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques.

RESULTS:

We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity in vitro.

CONCLUSION:

We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection in vitro. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted.

PMID:
27124730
PMCID:
PMC4849649
DOI:
10.1371/journal.pone.0154461
[Indexed for MEDLINE]
Free PMC Article

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