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• W4200425538 abstract "Chronic hepatitis B virus (HBV) infection (CHB) is a significant public health problem that could benefit from treatment with immunomodulators. Here we describe a set of therapeutic HBV vaccines that target the internal viral proteins.Vaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime only or prime-boost regimens. The HBV antigens are fused into an early T cell checkpoint inhibitor, herpes simplex virus (HSV) glycoprotein D (gD), which enhances and broadens vaccine-induced cluster of differentiation (CD8)+ T cell responses.Our results show that the vaccines are immunogenic in mice. They induce potent CD8+ T cell responses that recognize multiple epitopes. CD8+ T cell responses increase after a boost, although the breadth remains similar. In mice, which carry high sustained loads of HBV particles due to a hepatic infection with an adeno-associated virus (AAV)8 vector expressing the 1.3HBV genome, CD8+ T cell responses to the vaccines are attenuated with a marked shift in the CD8+ T cells' epitope recognition profile.Our data show that in different stains of mice including those that carry a human major histocompatibility complex (MHC) class I antigen HBV vaccines adjuvanted with a checkpoint inhibitor induce potent and broad HBV-specific CD8+ T cell responses and lower but still detectable CD4+ T cell responses. CD8+ T cell responses are reduced and their epitope specificity changes in mice that are chronically exposed to HBV antigens. Implications for the design of therapeutic HBV vaccines are discussed." @default.
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• W4200425538 date "2021-12-01" @default.
• W4200425538 modified "2023-09-25" @default.
• W4200425538 title "Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection" @default.
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• W4200425538 doi "https://doi.org/10.1186/s12985-021-01712-y" @default.
• W4200425538 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34876153" @default.
• W4200425538 hasPublicationYear "2021" @default.
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