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US 8,647,864 B2Granted
Compositions and methods for generating an immune response utilizing alphavirus-based vector systems
AssigneeNovartis AG
InventorsJohn M Polo, Thomas W Dubensky, Jr., Ilya Frolov, Jason P Gardner, Gillis Otten, Susan Barnett, David A Driver
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Abstract
Compositions and methods are provided for Eukaryotic Layered Vector Initiation Systems and Alphavirus replicon particles for introducing heterologous sequences into cells for generating immune responses.
Claims21
A eukaryotic layered vector initiation system, comprising:
- (a) a 5′ promoter capable of initiating in vivo the 5′ synthesis of alphavirus RNA from cDNA,
- (b) a sequence following the 5′ promoter which initiates transcription of alphavirus RNA,
- (c) a nucleic acid molecule which operably encodes all four alphaviral nonstructural proteins,
- (d) an alphavirus RNA polymerase recognition site, and
- (e) a 3′ polyadenylate tract,
- wherein the nucleic acid sequence which operably encodes all four alphaviral nonstructural proteins contains a mutation in at least non-structural protein 2 (nsp2), wherein the mutation is in one or more residues selected from the group consisting of residue 438, residue 622, and residue 634, numbered according to wild-type Sindbis nsp2 encoded by a nucleic acid molecule of SEQ ID NO:
- 1.
4 more elements
An alphavirus vector construct, comprising
- (a) a 5′ promoter which initiates synthesis of viral RNA in vitro from cDNA,
- (b) a 5′ sequence which initiates transcription of alphavirus RNA,
- (c) a nucleic acid molecule which operably encodes all four alphaviral nonstructural proteins,
- (d) an alphavirus RNA polymerase recognition sequence;
- and
- (e) a 3′polyadenylate tract,
- wherein the nucleic acid sequence which operably encodes all four alphaviral nonstructural proteins contains a mutation in at least non-structural protein 2 (nsp2), wherein the mutation is in one or more residues selected from the group consisting of residue 438, residue 622, and residue 634, numbered according to wild-type Sindbis nsp2 encoded by a nucleic acid molecule of SEQ ID NO:1.
4 more elements
An alphavirus RNA vector replicon capable of translation in a eukaryotic system, comprising
- (a) a 5′ sequence which initiates transcription of alphavirus RNA,
- (b) a nucleic acid molecule which operably encodes all four alphaviral nonstructural proteins,
- (c) an alphavirus RNA polymerase recognition sequence, and
- (d) a 3′ polyadenylate tract,
- wherein the nucleic acid sequence which operably encodes all four alphaviral nonstructural proteins contains a mutation in at least non-structural protein 2 (nsp2), wherein the mutation is in one or more residues selected from the group consisting of residue 438, residue 622, and residue 634, numbered according to wild-type Sindbis nsp2 encoded by a nucleic acid molecule of SEQ ID NO:1.
2 more elements
Dependencies are inferred from the claim text.