title: Woodchuck hepatitis virus core antigen-based DNA and protein vaccines induce qualitatively different immune responses that affect T cell recall responses and antiviral effects.
abstract: T helper type 1 (Th1) immunity was considered to play a dominant role in viral clearance of hepadnaviral infection. However, pre-primed Th2 type responses were able to efficiently control hepadnaviral infection in animal models. We investigated how pre-primed Th1/2 responses control hepadnaviral replication using the newly established mouse models. DNA (pWHcIm, pCTLA-4-C) and protein vaccines based on the nucleocapsid protein (WHcAg) of woodchuck hepatitis virus (WHV) primed specific immune responses with distinct features. The pre-primed responses determined the characteristics of recall responses if challenged with a WHcAg-expressing adenoviral vector. Vaccination with pWHcIm and pCTLA4-C facilitated viral control in the hydrodynamic injection model and reduced WHV loads by about 3 and 2 logs in WHV-transgenic mice, respectively, despite of different kinetics of specific CD8+ T cell responses. Thus, pre-primed Th2-biased responses facilitate the development of CD8+ T cell responses in mice compared with naïve controls and thereby confer better viral control.
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany; Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Ejuan
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Kosinska
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Dietze
authors.affiliation: Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Zhongji
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany; Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Baoju
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany. Electronic address: Mengji.lu@uni-due.de.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology; D005260:Female; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*; D019444:Vaccines, DNA / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014765:Viral Vaccines
keywords: DNA vaccination; Hepatitis B virus; T cell response; Virus-specific CD8+ T cells; Woodchuck hepatitis virus