TY  - JOUR
JF  - Vaccines
A1  - Chinnakannan, SK
A1  - Cargill, TN
A1  - Donnison, TA
A1  - Ansari, MA
A1  - Sebastian, S
A1  - Lee, LN
A1  - Hutchings, C
A1  - Klenerman, P
A1  - Maini, MK
A1  - Evans, T
A1  - Barnes, E
KW  - Hepatitis B virus (HBV); therapeutic HBV vaccine; T cell vaccine; chimpanzee adenovirus; ChAd; ChAdOx1; modified vaccinia Ankara; MVA
N2  - 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?, TNF-?, 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.
ID  - discovery10106038
UR  - https://doi.org/10.3390/vaccines8020184
IS  - 2
N1  - This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
TI  - The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
AV  - public
Y1  - 2020/06//
VL  - 8
ER  -