title: H5N1 influenza virus-like particle vaccine protects mice from heterologous virus challenge better than whole inactivated virus.
abstract: The highly pathogenic avian influenza (HPAI) H5N1 virus has become highly enzootic since 2003 and has dynamically evolved to undergo substantial evolution. Clades 2.3.2.1 and 2.3.4 have become the most dominant lineage in recent years, and H5N8 avian influenza outbreaks have been reported Asia. The current approach to generate influenza virus vaccines uses embryonated chicken eggs for large-scale production, although such vaccines have been poorly immunogenic to heterologous virus challenge. In the current study, virus-like particles (VLP) based on A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) and comprising hemagglutinin (HA), neuraminidase (NA), and matrix (M1) were produced using a baculovirus expression system to develop effective protection for different H5 HPAI clade challenges. Mice immunized with VLP demonstrated stronger humoral and cellular immune responses than mice immunized with whole influenza virus (WIV), with 20-fold higher IgG antibody titers against A/meerkat/Shanghai/SH-1/2012 after boost. Notably, the WIV vaccine group showed partial protection (80% survival) to homologous challenge, little protection (40% survival) to heterologous challenge, and 20% survival to H5N8 challenge, whereas all mice in the VLP+CFA group survived. These results provide insight for the development of effective prophylactic vaccines based on VLPs with cross-clade protection for the control of current H5 HPAI outbreaks in humans.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China; College of veterinary Medicine, Inner Mongolia Agricultural University, Inner Mongolia Autonomous Region, Huhhot, China.
authors.forename: Xianliang
authors.initials: X
authors.lastname: Ji
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin Province, China.
authors.forename: Lingnan
authors.initials: L
authors.lastname: Meng
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China; College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang Province, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Xuexing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Hualei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Changchun SR Biological Technology Co., Ltd, Changchun, Jilin Province, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Jin
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, China; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China. Electronic address: 13843027235@163.com.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, China; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China. Electronic address: xiaxzh@cae.cn.
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002642:Chick Embryo; D056738:Cross Protection; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle
keywords: Cross-protective; H5N1 influenza; Protection; Vaccine; Virus-like particles