title: Sequential immunization with consensus influenza hemagglutinins raises cross-reactive neutralizing antibodies against various heterologous HA strains.
abstract: Seasonal and emerging epidemics caused by influenza virus remain as a public health concern and an economic burden. The weak immunogenicity of conserved epitopes on hemagglutinin that induces broad protective immune responses is the main obstacle to the development of universal vaccines. In the present report, we designed the cross-subtypic sequential vaccination strategy and evaluated its neutralizing antibody (nAb) activity by pseudovirus-based neutralization assays. The results clearly indicated that compared with traditional vaccines strategy, the cross-subtypic sequential immunization could significantly induce a broad serum cross-reactive nAb response in mice as well as against homologous strains, and provide protection from heterologous virus PR8 (H1N1) challenge. Furthermore, we isolated two monoclonal antibodies from sequentially immunized mice, which had potent broadly neutralizing activity against multiple influenza strains. These data suggest the feasibility of sequential immunization in universal flu vaccine development.
authors.affiliation: Medical College of Soochow University, Suzhou, Jiangsu 215125, PR China; ENT Department of the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: VacDiagn Biotechnology, Suzhou, Jiangsu 215125, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, PR China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Medical College of Soochow University, Suzhou, Jiangsu 215125, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical College of Soochow University, Suzhou, Jiangsu 215125, PR China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, PR China. Electronic address: xujianqing@shphc.org.cn.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Medical College of Soochow University, Suzhou, Jiangsu 215125, PR China. Electronic address: hruisdm@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage* / Q000276:immunology*; D064789:Immunity, Heterologous; D007114:Immunization / Q000379:methods*; D009980:Influenza A virus / Q000276:immunology*; D008807:Mice, Inbred BALB C; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus
keywords: Influenza virus; Neutralizing antibody; Sequential immunization; Vaccine