title: A replicating modified vaccinia tiantan strain expressing an avian-derived influenza H5N1 hemagglutinin induce broadly neutralizing antibodies and cross-clade protective immunity in mice.
abstract: To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTTHA-QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies (Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination inhibition (HI) antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.
authors.affiliation: Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China ; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xiao
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China ; Department of Microbiology and Research Center of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Tan
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yu
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhan
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Du
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Microbiology and Research Center of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan ; The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, United States of America, and the The University of Hong Kong, Hong Kong SAR, China.
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.affiliation: Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China ; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China ; Department of Microbiology and Research Center of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism*; D000917:Antibody Formation / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D056738:Cross Protection; D004285:Dogs; D005260:Female; D006388:Hemagglutinins / Q000235:genetics*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D009976:Orthomyxoviridae Infections / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D006388:Hemagglutinins