Virus Neutralization by Human Intravenous Immunoglobulin Against Influenza Virus Subtypes A/H5 and A/H7

Abstract

Purpose

Highly pathogenic avian influenza viruses are a threat to human health. Although donor populations have not experienced pandemic, they have been immunized by natural infections and/or vaccinations of influenza viruses such as A/H1N1, A/H3N2, and B. Therefore, it is considered that human intravenous immunoglobulin (IVIG) derived from healthy donors does not include IgG against avian influenza viruses. However, cross-reactivity has not been evaluated yet. In this study, cross-reactivity against the avian influenza virus A/H5N1, A/H7N1, A/H7N2, A/H7N7, A/H7N9, and A/H10N9 was evaluated.

Materials and Methods

Several lots of IVIG derived from healthy donors in Japan were tested for virus neutralization using single- or multi-cycle virus neutralizing (S-VN or M-VN) assays that evaluate the infection-step associated with HA or the infection and propagation steps associated with HA and NA, respectively. In addition, anti-NA activities were evaluated by inhibiting the enzymatic activity in NAI assays.

Results

IVIG lots showed high neutralizing activities against three A/H5N1 strains in M-VN assays, whereas activities in S-VN assays were unstable. In addition, A/H7N2 was also neutralized in S-VN and M-VN assays, with higher activity in M-VN than in S-VN assays. A/H7N1 was neutralized in S-VN and M-VN assays. In contrast, weak or no activity against A/H7N7, A/H7N9, and A/H10N9 was observed in S-VN and M-VN assays. NAI assay results show that IVIG lots had inhibitory activities against N1 and N2; however, N2 activities differed depending on the strain. In contrast, no activities were observed against N7 and N9.

Conclusion

These results suggest that IVIG lots have neutralizing activity against avian influenza viruses during the virus propagation step, except for one strain, although no or weak activity was observed during the infection step.

Keywords:

• avian influenza virus
• A/H5
• A/H7
• neutralizing
• intravenous immunoglobulin

Acknowledgments

The authors thank Dr. Takeru Urayama and Mr. Shoji Ideno (Japan Blood Products Organization) and Dr. Hironori Yoshii (The Research Foundation for Microbial Diseases of Osaka University) for technical support.

Author Contributions

All authors have made a significant contribution to the work reported, that is, in the conception, study design, execution, acquisition of data, analysis and interpretation, and in drafting, revising or critically reviewing the article. All authors have given approval to the final version to be published; have agreed on the journal to which the article is being submitted; and have agreed to be accountable for all aspects of the work.

Disclosure

This study was funded by the Benesis Corporation (Currently Japan Blood Products Organization) and was conducted in part as a collaborative research project between Osaka University, The Research Foundation for Microbial Diseases of Osaka University, and the Benesis Corporation. Current affiliations are as follows: RK Koketsu, Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University; M Yunoki, Japan Blood Products Organization; Y Okuno and K Ikuta, Osaka Institute of Public Health. The authors declare no competing interests.