Hbv vaccines and methods treating hbv

A method of treating or preventing human hepatitis B virus (HBV) in a subject in need thereof, comprising administering to the subject a prime-boost regimen comprising administering a priming composition at a first time point and administering one or more boosting compositions at one or more subsequent time points, wherein the prime-boost regimen comprises:

• A) priming with a priming composition comprising an immunogenic composition comprising a first Pichinde mammarenavirus viral expression vector and a second Pichinde mammarenavirus viral expression vector, wherein:
• a) the first Pichinde mammarenavirus viral expression vector comprises a polynucleotide encoding a truncated HBV polymerase polypeptide comprising an inactivated reverse transcriptase domain and an inactivated RNase H, wherein the polypeptide is no longer than 600 amino acids in length and does not comprise all of the terminal protein (TP) domain and does not comprise all or part of the Spacer domain, wherein the polypeptide comprises or consists of an amino acid sequence of any one of SEQ ID NOs:
• 13-14;
• and
• b) the second Pichinde mammarenavirus viral expression vector comprises a polynucleotide encoding the a core-sAg fusion protein comprising in sequential order from the N-terminus to the C terminus, an HBV core polypeptide and an HBV small surface antigen (sAg) polypeptide, wherein the fusion protein is no longer than 450 amino acids in length, and wherein:
• i) the core polypeptide is from an HBV genotype B or C and the sAg i) polypeptide is from an HBV genotype C, wherein the fusion protein comprises or consists of an amino acid sequence of any one of SEQ ID NOs:
• 38-39, or an amino acid sequence that is at least 94%, 95%, 96%, 97%, 98% or 99% identical to the full length any one of SEQ ID NOs:
• 38-39;
• or
• ii) the core polypeptide is from an HBV genotype D and the sAg polypeptide is from an HBV genotype D, wherein the fusion protein comprises or consists of an amino acid sequence of any one of SEQ ID NOs:
• 40-41, or an amino acid sequence that is at least 97%, 98% or 99% identical to the full length any one of SEQ ID NOs:
• 40-41;
• and
• B) boosting with a boosting composition comprising an immunogenic composition comprising a first Lymphocytic choriomeningitis mammarenavirus (LCMV) viral expression vector and a second LCMV viral expression vector, wherein:
• a) the first LCMV arenavirus viral expression vector comprises a polynucleotide encoding a truncated HBV polymerase polypeptide comprising an inactivated reverse transcriptase domain and an inactivated RNase H, wherein the polypeptide is no longer than 600 amino acids in length and does not comprise all of the terminal protein (TP) domain and does not comprise all or part of the Spacer domain, wherein the polypeptide comprises or consists of an amino acid sequence of any one of SEQ ID NOs:
• 13-14;
• and
• b) the second LCMV arenavirus viral expression vector comprises a polynucleotide encoding the a core-sAg fusion protein comprising in sequential order from the N-terminus to the C terminus, an HBV core polypeptide and an HBV small surface antigen (sAg) polypeptide, wherein the fusion protein is no longer than 450 amino acids in length, and wherein:
• i) the core polypeptide is from an HBV genotype B or C and the sAg polypeptide is from an HBV genotype C, wherein the fusion protein comprises or consists of an amino acid sequence of any one of SEQ ID NOs:
• 38-39, or an amino acid sequence that is at least 94%, 95%, 96%, 97%, 98% or 99% identical to the full length any one of SEQ ID NOs:
• 38-39;
• or
• ii) the core polypeptide is from an HBV genotype D and the sAg polypeptide is from an HBV genotype D, wherein the fusion protein comprises or consists of an amino acid sequence of any one of SEQ ID NOs:
• 40-41, or an amino acid sequence that is at least 97%, 98% or 99% identical to the full length any one of SEQ ID NOs:
• 40-41.