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Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates
BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056916/ https://www.ncbi.nlm.nih.gov/pubmed/30041659 http://dx.doi.org/10.1186/s12985-018-1026-3 |
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author | Zhang, Xuefeng Wang, Jing Lu, Jing Li, Rongrong Zhao, Shuli |
author_facet | Zhang, Xuefeng Wang, Jing Lu, Jing Li, Rongrong Zhao, Shuli |
author_sort | Zhang, Xuefeng |
collection | PubMed |
description | BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6056916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60569162018-07-30 Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates Zhang, Xuefeng Wang, Jing Lu, Jing Li, Rongrong Zhao, Shuli Virol J Research BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-24 /pmc/articles/PMC6056916/ /pubmed/30041659 http://dx.doi.org/10.1186/s12985-018-1026-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Xuefeng Wang, Jing Lu, Jing Li, Rongrong Zhao, Shuli Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates |
title | Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates |
title_full | Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates |
title_fullStr | Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates |
title_full_unstemmed | Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates |
title_short | Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates |
title_sort | immunogenicity of adenovirus-vector vaccine targeting hepatitis b virus: non-clinical safety assessment in non-human primates |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056916/ https://www.ncbi.nlm.nih.gov/pubmed/30041659 http://dx.doi.org/10.1186/s12985-018-1026-3 |
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