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

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 IFNγ, TNF-α, 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.

Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

“…Our data suggests that T cell responses in IFNAR(-/-) mice vaccinated with ChAdOx1 and MVA viral vectors induce robust cellular Th1 immune responses. This is in agreement with previous works supporting the augmentation of T cell-mediated responses by MVA after a ChAdOx1 prime, in heterologous prime-boost strategies in both mice and human [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

Emerging Therapeutic Modalities against COVID-19

“…In a recent report, ChAdOx1 MERS capable of expressing the S protein of MERS-CoV was found to be safe and tolerated even at a high dose of 5 × 10 10 viral particles with minimum side effects in a phase 1 clinical trial [ 213 ]. It has also been reported to be effective as a vector to provide immunization against hepatitis B virus in mice [ 203 ]. Similarly, ChAdOX1 nCoV-19 encodes the S glycoprotein of novel SARS-CoV-2.…”

Designing the next‐generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures

“…Improvements of this strategy by targeting HBcAg instead HBsAg and addition of a TLR‐ligand (i.e. CpG) are currently in the pre‐clinical phase as are other combinations of prime and boost formulations targeting multiple HBV antigens such as chimpanzee adenoviral and MVA vectors or attenuated vesiculostomatitis virus‐based platforms 90,92,93 …”

“…CpG) are currently in the pre-clinical phase as are other combinations of prime and boost formulations targeting multiple HBV antigens such as chimpanzee adenoviral and MVA vectors or attenuated vesiculostomatitis virus-based platforms. 90,92,93 Adjuvants Adjuvants are in many cases crucial to prevent presentation of antigens in a tolerogenic context. It is important, however, to tailor the adjuvant to the mechanism of action and desired outcome of the TV platform.…”