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Short Report

J Mol Genet Med (December 2009), 3(2), 217-224

doi: jmgm

Published online: 23 December 2009

Full Text: (html | pdf ~330kb | refs)

Heterosubtypic anti-avian H5N1 influenza antibodies in intravenous immunoglobulins from globally separate populations protect against H5N1 infection in cell culture

John S Sullivan †‡, Paul W Selleck ¥, Teena Downton †, Ingrid Boehm ‡§, Anna-Maree Axell ¥, Yasmin Ayob ¶, Natalie M Kapitza †, Wayne Dyer §, Anna Fitzgerald ¢, Bradley Walsh ¢ and Garry W Lynch †ƒ€*

† Biosafety, Immunobiology, Global Health and Pandemic Infections Research, Central Clinical School, Faculty of Medicine, The University of Sydney, Camperdown, NSW 2006, Australia

‡ Children's Cancer Institute Australia for Medical Research, Randwick, NSW 2031, Australia

¥ The Australian Animal Health Laboratories, CSIRO, Geelong, Vic 3219, Australia

§ The Australian Red Cross Blood Service, 153 Clarence St, Sydney, NSW 2000, and Transfusion Medicine and Immunogenetics, Faculty of Medicine, University of Sydney, Camperdown, Sydney, NSW 2006, Australia

¶ The National Blood Centre, Kuala Lumpur, Malaysia

¢ Minomic Pty Ltd, PO Box 6126, Frenchs Forest, NSW 2086, Australia

ƒ Faculty of Veterinary Science, The University of Sydney, Camperdown, NSW 2006, Australia

€ Faculty of Dentistry, University of Sydney, Cellular and Molecular Pathology Research Unit, Oral Pathology and Oral Medicine, Westmead Centre for Oral Health, Westmead Hospital, NSW 2145, Australia

*Correspondence to: Garry Lynch, Email: garry_lynch@optusnet.com.au, Tel: +61 2 9519 8151, Fax: +61 2 9519 8151

Received: 31 August 2009, Revised: 08 DEcember 2009, Accepted: 11 December 2009

© Copyright The Authors

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ABSTRACT

With antigenically novel epidemic and pandemic influenza strains persistently on the horizon it is of fundamental importance that we understand whether heterotypic heterosubtypic antibodies gained from exposures to circulating human influenzas exist and can protect against emerging novel strains. From a background in transfusion medicine we have asked whether intravenous immunoglobulins (IVIGs) could provide an effective means to sample and understand heterotypic herd antibody immunity to influenza. Our studies of IVIG obtained from an infection-naive population (Australian) enabled us to reveal heterotypic heterosubtypic influenza antibodies that cross react with H5N1. We now expand those findings for an Australian donor population to include IVIG formulations from a variety of northern hemisphere populations. Examination of IVIGs from European and South East-Asian (Malaysian) blood donor populations further reveal heterotypic heterosubtypic antibodies to H5N1 in humans from different global regions. Importantly these protect against highly pathogenic avian H5N1 infection in vitro, albeit at low titres of inhibition. Although there were qualitative and quantitative differences in binding and protection between globally different formulations, the heterotypic heterosubtypic antibody activities for the respective IVIGs were in general quite similar. Of particular note because of the relative geographic proximity to the epicentre of H5N1 and the majority of human infections, was the similarity in the antibody binding responses between IVIGs from the Malayan peninsula, Europe and Australia. These findings highlight the value of employing IVIGs for the study of herd immunity, and particularly heterotypic heterosubtypic antibody responses to viral antigens such as those conserved between circulating human influenzas and emerging influenza strains such as H5N1. They also open a window into a somewhat ill defined arena of antibody immunity, namely heterotypic heterosubtypic immunity.

Keyswords: Heterosubtypic, antibody, IVIG, influenza, H5N1, H1N1, H3N2

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