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

doi:10.1371/journal.pone.0082740

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.

Highlights

H5N1 highly pathogenic avian influenza virus (HPAIV) infection in humans has been reported since 1997
H5N1 HPAIVs did not appear to transmit among humans, the public health risks associated with H5N1 HPAIVs remain unchanged since most humans do not possess immunity against H5N1 virus and H5N1 HPAIVs have been detected in poultry and swine [1,2], of which the latter is thought to be an origin of past pandemic virus [3,4,5]
We examined the pathogenicity of highly pathogenic avian influenza viruses, A/Vietnam/UT3040/2004 (H5N1) and A/whooper swan/Hokkaido/1/2008 (H5N1), in cynomolgus macaques

Summary

Introduction

H5N1 highly pathogenic avian influenza virus (HPAIV) infection in humans has been reported since 1997 (http://www. who.int/influenza/human_animal_interface/ H5N1_cumulative_table_archives/en/). H5N1 highly pathogenic avian influenza virus (HPAIV) infection in humans has been reported since 1997 H5N1 HPAIVs did not appear to transmit among humans Who.int/influenza/human_animal_interface/ Influenza_Summary_IRA_HA_interface_04Jun13.pdf), the public health risks associated with H5N1 HPAIVs remain unchanged since most humans do not possess immunity against H5N1 virus and H5N1 HPAIVs have been detected in poultry and swine [1,2], of which the latter is thought to be an origin of past pandemic virus [3,4,5]. It is thought that vaccine strains should be renewed according to circulating strains, and the development of a vaccine that is effective against a broad spectrum of different clades is required [9]

Methods

Results

Conclusion