INFECTIOUS HEPACIVIRUS PSEUDO-PARTICLES CONTAINING FUNCTIONAL e1, e2 ENVELOPE PROTEINS
AssigneesInstitut National De La Sante Et De La Recherche Medicale (Inserm), Ecole Normale Superieure De Lyon
InventorsBirke Bartosch, Francois-Loic Cosset
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Abstract
The invention relates to the generation and the use of hepacivirus pseudo-particles containing native functional E1, E2 envelope glycoproteins assembled onto retroviral core particles. These particles are highly infectious and constitute a valid model of hepacivirus virion.
Claims45
A method for producing infectious hepacivirus-like particles ex vivo comprising the steps of:
- providing a first nucleic acid sequence comprising a packaging competent retroviral-derived genome;
- providing a second nucleic acid sequence comprising a cDNA encoding core proteins from said retrovirus;
- providing a third nucleic acid sequence comprising a cDNA encoding a polyprotein comprising successively a signal peptide from a type I membrane protein, and a hepacivirus E1 protein and/or a hepacivirus E2 protein;
- transfecting host cells with said nucleic acid sequences and maintaining the transfected cells in culture for sufficient time to allow expression of the cDNAs to produce structural proteins from hepacivirus and retrovirus;
- and allowing the structural proteins to form virus-like particles.
The method according to any of preceding claims, wherein said nucleic acid sequence comprising a packaging competent retroviral-derived genome further comprises a transgene.
An infectious hepacivirus-like particle susceptible to be obtained by a method according to any of preceding claims, comprising the core proteins from a retrovirus, and a E1 hepacivirus glycoprotein and/or a E2 hepacivirus glycoprotein.
The infectious particle according to any of claims 14 to 23, wherein said retrovirus is selected from the group consisting of MLV, ALV, RSV, MPMV, HIV-1, HIV-2, Sly, EIAV, CAEV, or HFV.
Use of three nucleic acid sequences for the preparation of a medicament useful as a vaccine against hepatitis, wherein the nucleic acid sequences are:
- a first nucleic acid sequence comprising a packaging competent retroviral-derived genome;
- a second nucleic acid sequence comprising a cDNA encoding core proteins from said retrovirus;
- a third nucleic acid sequence comprising a cDNA encoding a polyprotein comprising successively a signal peptide from a type I membrane protein, and a hepacivirus E1 protein and/or a hepacivirus E2 protein;
- and, when transferred into cells of a subject, the nucleic acids sequences allow the production of structural proteins from hepacivirus and retrovirus, wherein the structural proteins form virus-like particles that are immunogenic.
A transformed host cell that contains:
- a first nucleic acid sequence comprising a packaging competent retrovirus-derived genome;
- a second nucleic acid sequence comprising a cDNA encoding the core proteins from said retrovirus;
- and
- a third nucleic acid sequence comprising a cDNA encoding a polyprotein comprising successively a signal peptide from a type 1 membrane protein, and a hepacivirus E1 protein and/or a hepacivirus E2 protein.
Dependencies are inferred from the claim text.