title: Characterization of Humoral Responses Induced by an H7N9 Influenza Virus-Like Particle Vaccine in BALB/C Mice.
abstract: In April 2013, human infections with a novel avian influenza (H7N9) virus emerged in China. It has caused serious concerns for public health throughout the world. However, there is presently no effective treatment, and an A (H7N9) H7 subtype influenza vaccine is not available. Vaccination with virus-like particles (VLPs) has showed considerable promise for many other subtype influenza viruses. To produce H7N9 VLPs, full length, unmodified hemagglutinin (HA), neuraminidase (NA), and matrix1 (M1) genes from the A/Wuxi/1/2013(H7N9) were cloned into a pCDNA5.1 FRT vector. By co-transfection, VLPs containing HA, NA, and M1 were secreted by 293T cells. VLPs were purified by ultracentrifugation and injected into mice by the intramuscular route. In animal experiments, humoral and cellular immunoresponse were all triggered by H7N9 VLPs. High levels of specific antibodies and the isotypes of IgG were detected by ELISA. Anamnestic cellular immune responses were examined by detecting specific cytotoxic T cell for IFN-Υ production in ELISPOT assay. The hemagglutination-inhibition (HAI) against the homologous virus was more than 1:64, and cross-reactive HAI titers against the heterologous virus (H1N1 and H3N2) were more than 1:16. Moreover, VLPs immunized mice showed a rapid increase of neutralizing antibodies, with neutralizing antibody titers more than 1:8, which increased four-fold against PBS immunized mice in week four. By week six, the mice had high neutralization ability against the given strain and held a potent homologous virus neutralizing capacity. Thus, VLPs represent a potential strategy for the development of a safe and effective vaccine against novel avian influenza (H7N9) virus.
authors.affiliation: Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Preventionand Control, Nanjing 210009, China. zhangli411@yeah.net.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of HIV/STD prevention and control, Jiangsu Provincial Center for Disease Preventionand Control, Nanjing 210009, China. hhtt319@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. chenyin1231@foxmail.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. shifengjuan905@163.com.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Shi
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. yuhy86@126.com.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. nestar1987@126.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. lbcui@njmu.edu.cn.
authors.forename: Lunbiao
authors.initials: L
authors.lastname: Cui
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. shizhiyang@jscdc.cn.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Key Laboratory of Enteric Pathogenic Microbiology, Ministry Health, Nanjing 210009, China. yongjunjiao@hotmail.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Preventionand Control, Nanjing 210009, China. huyuemei@hotmail.com.
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; D058425:Vaccines, Virus-Like Particle; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C109963:hemagglutinin, avian influenza A virus; D007371:Interferon-gamma; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: H7N9 avian influenza; cross-reactivity; neutralizing antibodies; vaccine; virus-like particles