Cargando…

Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant

Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Weidong, Zhao, Gan, Zhang, Shuren, Wang, Xianzheng, Yu, Xueping, Wang, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188151/
https://www.ncbi.nlm.nih.gov/pubmed/30344938
http://dx.doi.org/10.18632/oncotarget.25789
_version_ 1783363168554188800
author Zhao, Weidong
Zhao, Gan
Zhang, Shuren
Wang, Xianzheng
Yu, Xueping
Wang, Bin
author_facet Zhao, Weidong
Zhao, Gan
Zhang, Shuren
Wang, Xianzheng
Yu, Xueping
Wang, Bin
author_sort Zhao, Weidong
collection PubMed
description Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a 3-day pretreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) prior to a standard HBV vaccine. It achieved a 90% reduction of HBsAg level in the HBsAg transgenic mouse model. This protocol, while effective, remains too complex for clinical use. In this study, we formulated a new regimen by combining GM-CSF, IFN-α and a recombinant HBV vaccine (GM-CSF/IFN-α/VACCINE) into a single preparation and tested its efficacy in a HBV infection model. After four vaccinations, both serum HBeAg and HBsAg were cleared, accompanied by a 95% reduction of HBV(+) hepatocytes and the presence of a large number of infiltrating CD8(+) T cells in the liver. Mechanistically these robust responses were initiated by a vaccine-induced conversion of CCR2-dependent CD11b(+)Ly6C(hi) monocytes into CD11b(+)CD11c(+) DCs. This finding sheds light on the potential mechanism of action of the GM-CSF-based vaccine adjuvant and provides definable markers for clinical assessment during future testing of such highly potent vaccine protocols in HBV patients.
format Online
Article
Text
id pubmed-6188151
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-61881512018-10-21 Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant Zhao, Weidong Zhao, Gan Zhang, Shuren Wang, Xianzheng Yu, Xueping Wang, Bin Oncotarget Research Paper Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a 3-day pretreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) prior to a standard HBV vaccine. It achieved a 90% reduction of HBsAg level in the HBsAg transgenic mouse model. This protocol, while effective, remains too complex for clinical use. In this study, we formulated a new regimen by combining GM-CSF, IFN-α and a recombinant HBV vaccine (GM-CSF/IFN-α/VACCINE) into a single preparation and tested its efficacy in a HBV infection model. After four vaccinations, both serum HBeAg and HBsAg were cleared, accompanied by a 95% reduction of HBV(+) hepatocytes and the presence of a large number of infiltrating CD8(+) T cells in the liver. Mechanistically these robust responses were initiated by a vaccine-induced conversion of CCR2-dependent CD11b(+)Ly6C(hi) monocytes into CD11b(+)CD11c(+) DCs. This finding sheds light on the potential mechanism of action of the GM-CSF-based vaccine adjuvant and provides definable markers for clinical assessment during future testing of such highly potent vaccine protocols in HBV patients. Impact Journals LLC 2018-07-13 /pmc/articles/PMC6188151/ /pubmed/30344938 http://dx.doi.org/10.18632/oncotarget.25789 Text en Copyright: © 2018 Zhao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhao, Weidong
Zhao, Gan
Zhang, Shuren
Wang, Xianzheng
Yu, Xueping
Wang, Bin
Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant
title Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant
title_full Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant
title_fullStr Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant
title_full_unstemmed Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant
title_short Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant
title_sort clearance of hbeag and hbsag of hbv in mice model by a recombinant hbv vaccine combined with gm-csf and ifn-α as an effective therapeutic vaccine adjuvant
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188151/
https://www.ncbi.nlm.nih.gov/pubmed/30344938
http://dx.doi.org/10.18632/oncotarget.25789
work_keys_str_mv AT zhaoweidong clearanceofhbeagandhbsagofhbvinmicemodelbyarecombinanthbvvaccinecombinedwithgmcsfandifnaasaneffectivetherapeuticvaccineadjuvant
AT zhaogan clearanceofhbeagandhbsagofhbvinmicemodelbyarecombinanthbvvaccinecombinedwithgmcsfandifnaasaneffectivetherapeuticvaccineadjuvant
AT zhangshuren clearanceofhbeagandhbsagofhbvinmicemodelbyarecombinanthbvvaccinecombinedwithgmcsfandifnaasaneffectivetherapeuticvaccineadjuvant
AT wangxianzheng clearanceofhbeagandhbsagofhbvinmicemodelbyarecombinanthbvvaccinecombinedwithgmcsfandifnaasaneffectivetherapeuticvaccineadjuvant
AT yuxueping clearanceofhbeagandhbsagofhbvinmicemodelbyarecombinanthbvvaccinecombinedwithgmcsfandifnaasaneffectivetherapeuticvaccineadjuvant
AT wangbin clearanceofhbeagandhbsagofhbvinmicemodelbyarecombinanthbvvaccinecombinedwithgmcsfandifnaasaneffectivetherapeuticvaccineadjuvant