title: Preclinical evaluation of the safety and pathogenicity of a live attenuated recombinant influenza A/H7N9 seed strain and corresponding MF59-adjuvanted split vaccine.
abstract: Developing a safe and effective H7N9 influenza vaccine was initiated in early spring 2013, following human infections with a novel avian influenza A (H7N9) virus. In this study, a candidate H7N9 vaccine seed strain is produced using reverse genetics, with HA and NA derived from a human H7N9 virus and the remaining genes from the PR8 backbone virus which grows well in eggs. We verified that the virulence and transmissibility of the recombinant H7N9 vaccine seed strain were decreased as compared to wild-type H7N9 virus, to levels comparable with PR8. Using the seed virus, we produced a monovalent split influenza A (H7N9) MF59-adjuvanted vaccine that was immunogenic in mice. Our H7N9 vaccine is selected for clinical investigation and potential human use. To assess the safety of our H7N9 vaccine, we performed acute toxicity, repeated dose toxicity and active systemic anaphylaxis tests. Our results showed that, under the conditions used in this study, the NOEAL (no obvious adverse effect level) was 30 μg/0.5 mL.
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Huilin
authors: H
authors: Ou
authors: Department of Pre-clinical Research and Development, Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., Hangzhou, China.
authors: Wei
authors: W
authors: Yao
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Nanping
authors: N
authors: Wu
authors: Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Texas, USA.
authors: Frederick X C
authors: FX
authors: Wang
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Tianhao
authors: T
authors: Weng
authors: Department of Pre-clinical Research and Development, Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., Hangzhou, China.
authors: Chengcong
authors: C
authors: Han
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Xiangyun
authors: X
authors: Lu
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Dongshan
authors: D
authors: Yu
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Haibo
authors: H
authors: Wu
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Linfang
authors: L
authors: Cheng
authors: State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors: Honglin
authors: H
authors: Chen
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Hangping
authors: H
authors: Yao
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Lanjuan
authors: L
authors: Li
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002369:Castration; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005289:Ferrets; D006168:Guinea Pigs; D000071497:Immunogenicity, Vaccine; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008810:Mice, Inbred C57BL; D019055:No-Observed-Adverse-Effect Level; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011136:Polysorbates / Q000494:pharmacology* / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013185:Squalene / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000494:pharmacology; D014774:Virulence
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D013185:Squalene
keywords: H7N9; H7N9 seed strain; H7N9 vaccine; safety and toxicity