Research Papers:

Longevity of protective immune responses induced by a split influenza A (H7N9) vaccine mixed with MF59 adjuvant in BALB/c mice

Huilin Ou, Wei Yao, Dongshan Yu, Tianhao Weng, Frederick X.C. Wang, Xiaoxin Wu, Haibo Wu, Linfang Cheng, Xiangyun Lu, Nanping Wu, Honglin Chen, Lanjuan Li and Hangping Yao _

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Oncotarget. 2017; 8:91828-91840. https://doi.org/10.18632/oncotarget.20064

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Huilin Ou1,*, Wei Yao2,*, Dongshan Yu1,*, Tianhao Weng1, Frederick X.C. Wang3, Xiaoxin Wu1, Haibo Wu1, Linfang Cheng1, Xiangyun Lu1, Nanping Wu1, Honglin Chen4, Lanjuan Li1 and Hangping Yao1

1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

2 Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., Hangzhou, China

3 Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Dallas, Texas, USA

4 State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China

* These authors have contributed equally to this article

Correspondence to:

Hangping Yao, email:

Lanjuan Li, email:

Keywords: H7N9, adjuvant vaccine, MF59, immunogenicity, protective immune responses

Received: May 26, 2017 Accepted: July 29, 2017 Published: August 08, 2017


The influenza virus is a serious threat to public health worldwide. A novel avian influenza A (H7N9) virus with a mortality rate of approximately 30% has been identified as an unusually dangerous virus for humans by the World Health Organization. Pathogenic H7N9 continue to represent a public health concern, and several candidate vaccines are currently in development. We generated candidate H7N9 vaccine strains using reverse genetics, consisting of hemagglutinin and neuraminidase genes derived from a human H7N9 virus and the remaining genes from the PR8 (A/PuertoRico/8/34 (H1N1)) virus. This H7N9 vaccine exhibited superior efficacy when combined with MF59 compared to other adjuvants. Immunized BALB/c mice were followed to determine the duration of the protective immune response. Antibody levels decreased to between one-half and one-eighth of the peak values four months after the final dose of the vaccine. Previously vaccinated mice received an A/Zhejiang/DTID-ZJU01/2013 H7N9 challenge six months post-vaccination, and all remained protected. We also verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. The humoral immune response and Th2 cytokine production following influenza challenge was potently induced in the animals that received the split vaccine. Therefore, the split H7N9 influenza vaccine with the MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge even after six months.

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