Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates.

ABSTRACT: 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?×?109 viral particles (VP)/animal (low-dose group), 1.0?×?1010 VP/animal (mid-dose group), and 1.0?×?1011 VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0?×?1011 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)-? 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-? and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p?

SUBMITTER: Zhang X 

PROVIDER: S-EPMC6056916 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature