Lentiviral vectors for expression of hepatitis B virus (HBV) antigens

Inventors

JAMILUDDIN, Mohamad • BEJANARIU, Ana • SARRY, Emeline

Assignees

Theravectys SA

Abstract

The invention relates to nucleic acids, including lentiviral vectors and lentiviral vector particles, encoding at least one Hepatitis B virus (HBV) envelop surface of genotypes A and/or C antigen, at least one polymerase of genotypes A and/or C antigen, at least one HBX protein of genotypes A and/or C antigen, at least one HBV consensus core of genotypes A and/or C antigen, and at least one HBV consensus core MHCI and MHCII epitopes of genotypes A and/or C antigen. The invention encompasses these lentiviral vectors and lentiviral vector particles, methods of making the vectors, and their use, including medicinal uses. The lentiviral vectors and lentiviral vector particles are for use in administering to humans to induce immune responses against the HBV antigens.

Core Innovation

The described invention relates to lentiviral vectors and lentiviral vector particles for immunotherapy and prophylaxis of hepatitis B virus, in which the vector encodes hepatitis B virus components from genotype A antigen, genotype C antigen, or genotypes A and C. The encoded components include at least one HBV envelop surface antigen, at least one polymerase, at least one HBX protein, and at least one HBV consensus core.

The HBV consensus core is fused with MHCI/MHCII epitopes to drive an immune response goal. The document highlights a safety and efficacy rationale using specified lentiviral design features, including the absence of an enhancer and use of dendritic-cell focused promoters such as β2-microglobulin or MHC class I promoters, with optional elements including WPRE and cPPT/CTS.

The vector design also includes a self-inactivating ΔU3 LTR and packaging elements such as a χ packaging sequence, and production-related components such as VSV-G pseudotyping are described. Specific chimeric protein sequences identified by SEQ ID NO:24/25/26 are disclosed, and mouse immune response data is described in the context of intramuscular administration and CTL and T-cell response readouts, including HBV-3 IFN-γ ELISPOT and a prime-boost immunization context.

Claims Coverage

The partial document provides two independent claim types, a lentiviral vector and a lentiviral vector particle, each defined by a genotype-parameterized HBV payload and inclusion of at least one consensus-core MHCI and/or MHCII epitope. Across the independent claims, the inventive features focus on encoding genotype-selected HBV proteins and epitope-containing HBV consensus core elements within a lentiviral format.

Across the two independent claim formats, the core claim coverage is the encoding of genotype A and/or genotype C HBV components together with at least one HBV consensus core MHCI and/or MHCII epitope. Dependent claims in the provided excerpt further specify particular encoded sequences using SEQ ID NO:24/25 and add lentiviral particle/protein component requirements, plus coverage of isolated cells containing the claimed vector/vector particle and compositions containing the same.

Stated Advantages

Documented Applications