Rna replicon vaccines against hbv
AssigneeJanssen Sciences Ireland Unlimited Company
InventorsJason L. DEHART, Nathaniel Stephen WANG, Parinaz ALIAHMAD, Christian MAINE, Heather Lynn DAVIS, Craig PACE
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Abstract
Nucleic acid molecules encoding hepatitis B virus (HBV) surface antigens, HBV core antigens, and HBV polymerase antigens, and related combinations, are described. Also described are vectors, such as DNA plasmids or viral vectors, and RNA replicons, expressing the HBV antigens, and pharmaceutical compositions containing the expression vectors. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the pharmaceutical compositions of the invention are also described.
Claims42
A nucleic acid combination comprising a first non-naturally occurring polynucleotide sequence comprising, ordered from the 5′- to 3′-end:
- (1) a polynucleotide sequence encoding a first hepatitis B virus (HBV) antigen,
- (2) a first internal ribosome entry sequence (IRES) element or a polynucleotide sequence encoding a first autoprotease peptide, and
- (3) a polynucleotide sequence encoding a second HBV antigen, and
- a second non-naturally occurring polynucleotide sequence comprising, ordered from the 5′- to 3′-end:
- (1) a polynucleotide sequence encoding a third hepatitis B virus (HBV) antigen,
- (2) a second internal ribosome entry sequence (IRES) element or a polynucleotide sequence encoding a second autoprotease peptide, and
- (3) a polynucleotide sequence encoding a fourth HBV antigen,
- wherein the first and second non-naturally occurring polynucleotide sequence are linked by a third internal ribosome entry sequence (IRES) element or a polynucleotide sequence encoding a third autoprotease peptide, or are present in separate nucleic acid molecules, and
- wherein the first, second, third and fourth HBV antigens are each independently selected from the group consisting of an HBV core antigen, an HBV polymerase (pol) antigen, and an HBV surface antigen, and at least one of the first, second, third and fourth HBV antigens is an HBV surface antigen selected from an HBV Pre-S1 antigen having an amino acid sequence at least 98% identical to the amino acid sequence of SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and an HBV PreS2.S antigen having an amino acid sequence at least 98% identical to the amino acid sequence of SEQ ID NO:
- 5.
An RNA replicon comprising the polynucleotide sequence of any one of SEQ ID NOs:
- 65 to 72.
Dependencies are inferred from the claim text.