Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge

Abstract Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we develo...

Full description

Bibliographic Details
Main Authors: Xiang Wang, Weihui Fu, Songhua Yuan, Xi Yang, Yufeng Song, Lulu Liu, Yudan Chi, Tao Cheng, Man Xing, Yan Zhang, Chao Zhang, Yong Yang, Caihong Zhu, Xiaoyan Zhang, Sidong Xiong, Jianqing Xu, Dongming Zhou
Format: Article
Language:English
Published: Nature Publishing Group 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02019-1
id doaj-01fc40478339433a96e030a84ab2587f
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Xiang Wang
Weihui Fu
Songhua Yuan
Xi Yang
Yufeng Song
Lulu Liu
Yudan Chi
Tao Cheng
Man Xing
Yan Zhang
Chao Zhang
Yong Yang
Caihong Zhu
Xiaoyan Zhang
Sidong Xiong
Jianqing Xu
Dongming Zhou
spellingShingle Xiang Wang
Weihui Fu
Songhua Yuan
Xi Yang
Yufeng Song
Lulu Liu
Yudan Chi
Tao Cheng
Man Xing
Yan Zhang
Chao Zhang
Yong Yang
Caihong Zhu
Xiaoyan Zhang
Sidong Xiong
Jianqing Xu
Dongming Zhou
Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
Scientific Reports
author_facet Xiang Wang
Weihui Fu
Songhua Yuan
Xi Yang
Yufeng Song
Lulu Liu
Yudan Chi
Tao Cheng
Man Xing
Yan Zhang
Chao Zhang
Yong Yang
Caihong Zhu
Xiaoyan Zhang
Sidong Xiong
Jianqing Xu
Dongming Zhou
author_sort Xiang Wang
title Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
title_short Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
title_full Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
title_fullStr Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
title_full_unstemmed Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
title_sort both haemagglutinin-specific antibody and t cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza h7n9 viral challenge
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-05-01
description Abstract Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+ T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.
url https://doi.org/10.1038/s41598-017-02019-1
work_keys_str_mv AT xiangwang bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT weihuifu bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT songhuayuan bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT xiyang bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT yufengsong bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT lululiu bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT yudanchi bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT taocheng bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT manxing bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT yanzhang bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT chaozhang bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT yongyang bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT caihongzhu bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT xiaoyanzhang bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT sidongxiong bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT jianqingxu bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
AT dongmingzhou bothhaemagglutininspecificantibodyandtcellresponsesinducedbyachimpanzeeadenoviralvaccineconferprotectionagainstinfluenzah7n9viralchallenge
_version_ 1724392614221840384
spelling doaj-01fc40478339433a96e030a84ab2587f2020-12-08T03:20:00ZengNature Publishing GroupScientific Reports2045-23222017-05-017111110.1038/s41598-017-02019-1Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challengeXiang Wang0Weihui Fu1Songhua Yuan2Xi Yang3Yufeng Song4Lulu Liu5Yudan Chi6Tao Cheng7Man Xing8Yan Zhang9Chao Zhang10Yong Yang11Caihong Zhu12Xiaoyan Zhang13Sidong Xiong14Jianqing Xu15Dongming Zhou16Institute of Biology and Medical Sciences, Soochow UniversityShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Fudan UniversityShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Fudan UniversityVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesInstitute of Biology and Medical Sciences, Soochow UniversityVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Fudan UniversityInstitute of Biology and Medical Sciences, Soochow UniversityShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Fudan UniversityVaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesAbstract Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+ T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.https://doi.org/10.1038/s41598-017-02019-1