Hepatitis C virus nucleic acid vaccine
Inventors
Colloca, Stefano • Folgori, Antonella • Lahm, Armin • Nicosia, Alfredo
Assignees
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Publication Number
US-9056090-B2
Publication Date
2015-06-16
Expiration Date
Abstract
The present invention features nucleic acid constructs that can be used as a HCV nucleic acid vaccine, vaccine component, or in the production of a HCV vaccine. Described constructs include those: (1) encoding for a chimeric HCV polypeptide containing a NS3-4A region based on a first HCV strain and an NS3-NS4A-NS4B-NS5A or an NS3-NS4A-NS4B-NS5A-NS5B region based on a second strain; and (2) a chimpanzee based adenovector encoding an HCV polypeptide.
Core Innovation
The invention concerns a nucleic acid HCV vaccine and recombinant adenovector constructs encoding chimeric hepatitis C virus (HCV) non-structural proteins. The HCV polypeptide comprises HCV NS3-NS4A-NS4B-NS5A, and related embodiments include additional NS5B in a manner that yields enzymatically inactive NS5B through self-processing.
The adenovector platform uses chimpanzee adenovectors, including ChAd3 and ChAd63, built on an adenovirus genome containing an E1 deletion, an E3 deletion, and an optional E4 deletion. In some embodiments, the E4 region is handled via an E4 deletion and an Ad5 E4orf6 substitution.
Expression cassettes are described as encoding the HCV polypeptide and being positioned in relation to the E1 or E3 deletion. The document describes gene cassette and regulatory elements for these expression cassettes, together with vector design elements including fiber, hexon, and penton regions with stated sequence identity relationships to reference SEQ ID NOs.
Claims Coverage
The partial content includes one independent claim, directed to a recombinant adenovector with an HCV NS3-NS4A-NS4B-NS5A expression cassette and a specified E1/E3/E4 deletion adenovirus genome having fiber, hexon, and penton regions meeting defined sequence identity thresholds. The independent claim centers on four inventive features.
HCV NS3-NS4A-NS4B-NS5A expression cassette in a recombinant adenovector
An expression cassette encoding an HCV polypeptide, wherein the HCV polypeptide comprises HCV NS3-NS4A-NS4B-NS5A; and wherein the expression cassette is located at either the E1 or E3 deletion.
Adenovirus genome with E1 deletion, E3 deletion, and optional E4 deletion for an adenovector
An adenovirus genome containing an E1 deletion, an E3 deletion, and an optional E4 deletion.
Sequence-identity thresholds for fiber, hexon, and penton regions
A fiber region with an amino acid sequence having an identity of at least 70% to SEQ ID NO: 3 or of at least 80% to SEQ ID NO: 9; a hexon region with an amino acid sequence having an identity of at least 95% to either SEQ ID NO: 5 or 11; and a penton region with an amino acid sequence having an identity of at least 85% to SEQ ID NO: 7.
Overall, the independent claim requires a recombinant adenovector that combines an HCV NS3-NS4A-NS4B-NS5A expression cassette positioned at the E1 or E3 deletion with an adenovirus genome carrying E1 deletion and E3 deletion and optional E4 deletion, while also enforcing minimum sequence identity thresholds for the fiber, hexon, and penton regions.
Stated Advantages
Induction of cell-mediated immunity measured by IFN-γ ELISPOT in mice.
Expression and genetic stability of the constructs are described.
Boosted heterologous prime-boost immunogenicity in non-human primates is described.
Documented Applications
Immunogenicity assessment in mice via induction of cell-mediated immunity measured by IFN-γ ELISPOT.
Heterologous prime-boost regimens and immune responses in non-human primates are described.
Treatment or prophylaxis of hepatitis C via administration of a therapeutically active amount of a recombinant adenovector.
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