title: Protective efficacy and hepatitis B virus clearance in mice enhanced by cell-mediated immunity with novel prime-boost regimens.
abstract: In this study, anti-hepatitis B virus (HBV) immunity was evaluated in mice using several regimens of the HBV recombinant protein vaccine HBSS1 that expressed in CHO cells containing S (1-223 aa) and preS1 (21-47 aa) and recombinant adenovirus rAdSS1 vaccine. Further, the protective efficacy of these vaccine regimens was studied in a mouse model. High titres of antigen-specific antibodies and neutralizing activity were elicited in mice after vaccination. However, robust multi-antigen (preS1 and S)-specific cell-mediated immunity (CMI) was only detected in mice primed with HBSS1 and boosted with rAdSS1. Moreover, functional T-cell responses with high levels of cytokines and antigen-specific cytotoxic T-cell responses (CD107a+CD8+) were also detected in the mice. Rapid clearance of hepatitis B surface antigen and HBV DNA in blood and significantly decreased hepatitis B envelope antigen levels were observed in mice immunized with the heterogeneous prime-boost vaccine after hepatitis B virus challenge by hydrodynamic injection (HI) of pCS-HBV1.3. The clearance of HBV correlated well with antigen-specific CMI (Th1 and CTL responses) and cytokine profiles (IFN-γ, TNF-α, IL-2) elicited by vaccination. Taken together, our results might contribute to the development of new human HBV vaccines and a better understanding of the mechanisms underlying immune protection and clearance of hepatitis B virus infection.
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.|Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Heibei Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Chuai
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Ruan
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Tan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007111:Immunity, Cellular; D007115:Immunization Schedule; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: hepatitis B virus; immunity; mice; prime-boost; vaccine