1. The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors
- Author
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Chinnakannan, Senthil K., Cargill, Tamsin N., Donnison, Timothy A., Ansari, M. Azim, Sebastian, Sarah, Lee, Lian Ni, Hutchings, Claire, Klenerman, Paul, Maini, Mala K., Evans, Tom, and Barnes, Eleanor
- Subjects
T cell vaccine ,ChAd ,modified vaccinia Ankara ,viruses ,virus diseases ,Hepatitis B virus (HBV) ,ChAdOx1 ,therapeutic HBV vaccine ,MVA ,chimpanzee adenovirus ,digestive system diseases - Abstract
Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy, novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFN&gamma, TNF-&alpha, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection.
- Published
- 2020
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