Influenza-Specific Antibody-Dependent Phagocytosis

Fernanda Ana-Sosa-Batiz; Hillary Vanderven; Sinthujan Jegaskanda; Angus Johnston; Steven Rockman; Karen Laurie; Ian Barr; Patrick Reading; Marit Lichtfuss; Stephen J Kent

doi:10.1371/journal.pone.0154461

Influenza-Specific Antibody-Dependent Phagocytosis

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

Authors

Fernanda Ana-Sosa-Batiz¹, Hillary Vanderven¹, Sinthujan Jegaskanda¹, Angus Johnston^{2

3}, Steven Rockman^{1

4}, Karen Laurie⁵, Ian Barr⁵, Patrick Reading^{1

5}, Marit Lichtfuss¹, Stephen J Kent^{1

6

7}

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / biosynthesis*
Antibodies, Neutralizing / pharmacology
Antibodies, Viral / biosynthesis*
Antibodies, Viral / pharmacology
Cell Line
Cross Protection
Cross Reactions
Fluorescent Dyes / chemistry
Hemagglutination Inhibition Tests
Hemagglutinin Glycoproteins, Influenza Virus / chemistry
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Humans
Immobilized Proteins / chemistry
Immobilized Proteins / immunology
Immune Sera / chemistry
Immune Sera / pharmacology
Immunity, Humoral*
Immunoglobulins, Intravenous / pharmacology
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H3N2 Subtype / immunology
Macaca nemestrina
Microspheres
Monocytes / drug effects
Monocytes / immunology*
Monocytes / virology
Orthomyxoviridae Infections / immunology*
Orthomyxoviridae Infections / virology
Phagocytosis / drug effects*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Fluorescent Dyes
Hemagglutinin Glycoproteins, Influenza Virus
Immobilized Proteins
Immune Sera
Immunoglobulins, Intravenous

Grants and funding

This work was supported by the Australian National Health and Medical Research Council [SJK 628331, 1023294, and 510488; https://www.nhmrc.gov.au/]. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health [http://www.health.gov.au/]. The funder provided support in the form of salaries for authors SJK, SJ, KL, IB, and PR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.