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Biologics. 2017 Mar 10;11:23-30. doi: 10.2147/BTT.S123831. eCollection 2017.

Neutralizing activities against seasonal influenza viruses in human intravenous immunoglobulin.

Biologics : targets & therapy

Hiroyuki Onodera, Takeru Urayama, Kazue Hirota, Kazuhiro Maeda, Ritsuko Kubota-Koketsu, Kazuo Takahashi, Katsuro Hagiwara, Yoshinobu Okuno, Kazuyoshi Ikuta, Mikihiro Yunoki

Affiliations

  1. Medical Information Department.
  2. Research and Development Division, Japan Blood Products Organization, Tokyo.
  3. Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa.
  4. Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa; Former Department of Virology, Research Institute for Microbial Diseases, Osaka University.
  5. Virology Division, Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka.
  6. Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
  7. Research and Development Division, Japan Blood Products Organization, Tokyo; Former Department of Virology, Research Institute for Microbial Diseases, Osaka University; Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.

PMID: 28331286 PMCID: PMC5354529 DOI: 10.2147/BTT.S123831

Abstract

Influenza viruses A/H1N1, A/H3N2, and B are known seasonal viruses that undergo annual mutation. Intravenous immunoglobulin (IVIG) contains anti-seasonal influenza virus globulins. Although the virus-neutralizing (VN) titer is an indicator of protective antibodies, changes in this titer over extended time periods have yet to be examined. In this study, variations in hemagglutination inhibition (HI) and VN titers against seasonal influenza viruses in IVIG lots over extended time periods were examined. In addition, the importance of monitoring the reactivity of IVIG against seasonal influenza viruses with varying antigenicity was evaluated. A/H1N1, A/H3N2, and B influenza virus strains and IVIG lots manufactured from 1999 to 2014 were examined. The HI titer was measured by standard methods. The VN titer was measured using a micro-focus method. IVIG exhibited significant HI and VN titers against all investigated strains. Our results suggest that the donor population maintains both specific and cross-reactive antibodies against seasonal influenza viruses, except in cases of pandemic viruses, despite major antigen changes. The titers against seasonal influenza vaccine strains, including past strains, were stable over short time periods but increased slowly over time.

Keywords: IVIG; influenza; neutralization; seasonal; vaccine

Conflict of interest statement

Disclosure H. Onodera, T. Urayama, and M. Yunoki are employees of the Japan Blood Products Organization. T. Urayama and M. Yunoki are also former employees of the Benesis Corporation. H. Onodera is a

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