Protective Role of Human Intravenous Immunoglobulin from Influenza A Virus Infection in Mice

Katsuro Hagiwara1, *, Sachiyo Kawami1, Yuuko Kato-Mori1, Ritsuko Kubota-Koketsu2, 5, Muneo Tsujikawa3, Takeru Urayama2, 3, Mikihiro Yunoki1, 2, 3, #, *, Kazuo Takahashi4, Kazuyoshi Ikuta2
1 School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan
2 Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3 Osaka Research Laboratory, Benesis Corporation, Osaka, Japan
4 Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka, Japan
5 Kanonji Institute, The Research Foundation For Microbial Diseases of Osaka University, Kagawa, Japan

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© 2012 Hagiwara et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to these authors at the School of Veterinary Medicine, Rakuno Gakuen University. 582 Midorimachi, Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan; Tel: +81-11-388-4826; Fax: +81-11-387-5890; E-mail: and Pathogenic Risk Management, Benesis Corporation. 2-6-18, Kitahama, Chuo-ku, Osaka, Osaka 541-8505, Japan; Tel: +81-6-6201-1679; Fax: +81-6-6231-4191; E-mail:
# Current address of M. Yunoki: Pathogenic Risk Management, Benesis Corp


Intravenous immunoglobulin (IVIG) has been manufactured from pooled plasma of 10,000 or more units from healthy donors. Recently, we reported that the IVIG manufactured even before the 2009 influenza pandemic contained antibodies reactive to seasonal H1N1 and pandemic H1N1 2009 (H1N1 pdm) viruses. In this study, we used an animal model to evaluate the efficacy of IVIG against influenza infections. A seasonal influenza H1N1 strain (New Caledonia, A/NC/20/99) and an H1N1 pdm strain (A/Osaka/168/2009) were used. The BALB/c and severe combined immunodeficiency mice (SCID; C.B-17/lcr-scid/scid) were also used. Mice inoculated with A/NC/20/99 or A/Osaka/168/2009 were administrated IVIG and monitored for 3 weeks. The administration of IVIG 48 h before and after inoculation with a mouse-adapted seasonal H1N1 virus, resulted in survival rates of 80 and 88%, respectively. The rate among control mice was 30%. In addition, infectivity in lungs from IVIG-treated mice also decreased significantly. Similar effects of IVIG on the survival rate were obtained with H1N1 pdm. Thus, IVIG was shown to be effective against both viruses in mice.

Keywords: IVIG, Influenza, 2009 Pandemic Influenza, Animal model.