Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine

Misako Nakayama; Shintaro Shichinohe; Yasushi Itoh; Hirohito Ishigaki; Mitsutaka Kitano; Masahiko Arikata; Van Loi Pham; Hideaki Ishida; Naoko Kitagawa; Masatoshi Okamatsu; Yoshihiro Sakoda; Takaya Ichikawa; Hideaki Tsuchiya; Shinichiro Nakamura; Quynh Mai Le; Mutsumi Ito; Yoshihiro Kawaoka; Hiroshi Kida; Kazumasa Ogasawara

doi:10.1371/journal.pone.0082740

Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine

PLoS One. 2013 Dec 23;8(12):e82740. doi: 10.1371/journal.pone.0082740. eCollection 2013.

Authors

Misako Nakayama¹, Shintaro Shichinohe², Yasushi Itoh¹, Hirohito Ishigaki¹, Mitsutaka Kitano¹, Masahiko Arikata³, Van Loi Pham¹, Hideaki Ishida¹, Naoko Kitagawa¹, Masatoshi Okamatsu², Yoshihiro Sakoda², Takaya Ichikawa², Hideaki Tsuchiya⁴, Shinichiro Nakamura⁴, Quynh Mai Le⁵, Mutsumi Ito⁶, Yoshihiro Kawaoka⁷, Hiroshi Kida⁸, Kazumasa Ogasawara¹

Affiliations

¹ Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
² Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
³ Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan ; Department of Otorhinolaryngology-Head and Neck Surgery, Shiga University of Medical Science, Otsu, Japan.
⁴ Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Japan.
⁵ National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
⁶ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁷ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan ; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
⁸ Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan ; Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.

Abstract

H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

Publication types

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

MeSH terms

Animals
Antibodies, Viral / immunology
Antibody Formation / immunology
Birds / virology
Body Temperature
Female
Humans
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H1N1 Subtype / pathogenicity*
Influenza A Virus, H5N1 Subtype / immunology
Influenza A Virus, H5N1 Subtype / pathogenicity*
Influenza Vaccines / immunology*
Influenza, Human / epidemiology*
Influenza, Human / immunology
Influenza, Human / prevention & control
Influenza, Human / virology
Macaca fascicularis / immunology
Macaca fascicularis / virology*
Neuraminidase / antagonists & inhibitors
Neuraminidase / metabolism
Neutralization Tests
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / prevention & control*
Orthomyxoviridae Infections / virology
Pandemics
T-Lymphocytes / immunology
Vaccination
Vaccines, Inactivated / immunology*
Viral Load

Substances

Antibodies, Viral
Influenza Vaccines
Vaccines, Inactivated
Neuraminidase

Grants and funding

This work was supported by Regional Research and Development Resources Utilization Program, Japan Science and Technology Agency, the Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan, for Joint Research Program of the Research Center for Zoonosis Control, Hokkaido University and the Japan Initiative for Global Research Network on Infectious Diseases. The funders had no role in study design, data collecton and analysis, decision to publish, or preparation of the manuscript.