Development of a high-yield reassortant influenza vaccine virus derived from the A/Anhui/1/2013 (H7N9) strain

Kazuya Nakamura; Masayuki Shirakura; Yasushi Suzuki; Tadasuke Naito; Seiichiro Fujisaki; Masato Tashiro; Eri Nobusawa

doi:10.1016/j.vaccine.2015.11.050

Development of a high-yield reassortant influenza vaccine virus derived from the A/Anhui/1/2013 (H7N9) strain

Vaccine. 2016 Jan 12;34(3):328-33. doi: 10.1016/j.vaccine.2015.11.050. Epub 2015 Dec 1.

Authors

Kazuya Nakamura¹, Masayuki Shirakura¹, Yasushi Suzuki¹, Tadasuke Naito¹, Seiichiro Fujisaki¹, Masato Tashiro¹, Eri Nobusawa²

Affiliations

¹ Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan.
² Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan. Electronic address: nobusawa@nih.go.jp.

PMID: 26657023
DOI: 10.1016/j.vaccine.2015.11.050

Abstract

In April 2013, the first three fatal cases of human infection with an avian influenza A virus (H7N9) were reported in China. Because of a pandemic threat by this virus, we have commenced to develop candidate vaccine viruses (CVVs). Three 6:2 genetic reassortant viruses with different hemagglutinin (HA) sequences, NIIDRG-10, -10.1 and -10.2, were generated by a reverse genetics technique between the high egg-growth master virus, A/Puerto Rico/8/34 (H1N1) and A/Anhui/1/2013 (H7N9), kindly provided by the Chinese Center for Disease Control and Prevention. The different HA gene sequences of the three CVVs were derived from the original virus stock. NIIDRG-10 possesses HA, whose sequence is identical to that of the original A/Anhui/1/2013 (H7N9) in the Global Initiative on Sharing Avian Influenza Data (EPI439507), while NIIDRG-10.1 and -10.2 possess amino acid differences, A125T and N123D/N149D, respectively, compared with NIIDRG-10. NIIDRG-10 replicated in embryonated chicken eggs with low hemagglutination titer 128, whereas NIIDRG-10.1 and -10.2 grew well with hemagglutination titer 1024. These viruses reacted well with a ferret antiserum raised against the original A/Anhui/1/2013 virus. Ferret antiserum against NIIDRG-10.1 reacted well with A/Anhui/1/2013 similar to the homologous virus NIIDRG-10.1. These results indicated that NIIDRG-10.1 passed the two-way test of antigenic identity. In contrast, the ferret antiserum against NIIDRG-10.2 reacted with A/Anhui/1/2013 at an 8-fold lower hemagglutination inhibition titer than with the homologous virus NIIDRG-10.2, indicating an antigenic change. The total and HA protein yields of NIIDRG-10.1 were 14.7 and 6.9 μg/ml, respectively, similar to those levels of high-yield seed viruses of seasonal influenza vaccines. NIIDRG-10.1 was approved as one of the CVVs for H7N9 viruses by the WHO in 2013. The candidate vaccine derived from NIIDRG-10.1 is currently being evaluated in a phase II clinical study in Japan.

Keywords: Avian influenza A (H7N9) virus; Candidate vaccine virus; Viral quasi-species.

Publication types

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

MeSH terms

Animals
Antibodies, Viral / blood
Clinical Trials, Phase II as Topic
Ferrets
Hemagglutination Tests
Humans
Influenza A Virus, H7N9 Subtype / genetics
Influenza A Virus, H7N9 Subtype / immunology*
Influenza Vaccines / administration & dosage*
Influenza Vaccines / genetics
Influenza Vaccines / immunology*
Influenza Vaccines / isolation & purification
Japan
Reassortant Viruses / genetics
Reassortant Viruses / immunology*
Reverse Genetics

Substances

Antibodies, Viral
Influenza Vaccines