Tri-segmented pichinde viruses as vaccine vectors
AssigneesHookipa Biotech GmbH, UniversitäT Basel
InventorsWeldi Bonilla, Daniel David Pinschewer, Klaus Orlinger
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Abstract
The present application relates to Pichinde viruses with rearrangements of their open reading frames (“ORF”) in their genomes. In particular. described herein is a modified Pichinde virus genomic segment, wherein the Pichinde virus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented Pichinde virus particles comprising one L segment and two S segments or two L segments and one S segment. The Pichinde virus, described herein may be suitable for vaccines md/or treatment of diseases and/or for the use in immunotherapies.
Claims71
A Pichinde virus genomic segment, wherein the genomic segment is engineered to carry a viral open reading frame (“ORF”) in a position other than the wild-type position of the ORF, wherein the Pichinde virus genomic segment is selected from the group consisting of:
- (i) an S segment, wherein the ORF encoding the nucleoprotein (“NP”) is under control of a Pichinde virus 5′ untranslated region (“UTR”);
- (ii) an S segment, wherein the ORF encoding the matrix protein Z (“Z protein”) is under control of a Pichinde virus 5′ UTR;
- (iii) an S segment, wherein the ORF encoding the RNA dependent RNA polymerase L (“L protein”) is under control of a Pichinde virus 5′ UTR;
- (iv) an S segment, wherein the ORF encoding the viral glycoprotein (“GP”) is under control of a Pichinde virus 3′ UTR;
- (v) an S segment, wherein the ORF encoding the L protein is under control of a Pichinde virus 3′ UTR;
- (vi) an S segment, wherein the ORF encoding the Z protein is under control of a Pichinde virus 3′ UTR;
- (vii) an L segment, wherein the ORF encoding the GP is under control of a Pichinde virus 5′ UTR;
- (viii) an L segment, wherein the ORF encoding the NP is under control of a Pichinde virus 5′ UTR;
- (ix) an L segment, wherein the ORF encoding the L protein is under control of a Pichinde virus 5′ UTR;
- (x) an L segment, wherein the ORF encoding the GP is under control of a Pichinde virus 3′ UTR;
- (xi) an L segment, wherein the ORF encoding the NP is under control of a Pichinde virus 3′ UTR;
- and
- (xii) an L segment, wherein the ORF encoding the Z protein is under control of a Pichinde virus 3′ UTR.
A tri-segmented Pichinde virus particle comprising one L segment and two S segments, wherein propagation of the tri-segmented Pichinde virus particle does not result in a replication-competent bi-segmented viral particle after 70 days of persistent infection in mice lacking type I interferon receptor, type II interferon receptor and recombination activating gene 1 (RAG1) and having been infected with 104 PFU of the tri-segmented Pichinde virus particle.
A tri-segmented Pichinde virus particle comprising two L segments and one S segment, wherein propagation of the tri-segmented Pichinde virus particle does not result in a replication-competent bi-segmented viral particle after 70 days of persistent infection in mice lacking type I interferon receptor, type II interferon receptor and recombination activating gene 1 (RAG1) and having been infected with 104 PFU of the tri-segmented Pichinde virus particle.
A tri-segmented Pichinde virus particle comprising one L segment and two S segments, wherein a first S segment is engineered to carry an ORF encoding GP in a position under control of a Pichinde virus 3′ UTR and an ORF encoding a first gene of interest in a position under control of a Pichinde virus 5′ UTR and a second S segment is engineered to carry an ORF encoding NP in a position under control of a Pichinde virus 3′ UTR and an ORF encoding a second gene of interest in a position under control of a Pichinde virus 5′ UTR.
A tri-segmented Pichinde virus particle comprising one L segment and two S segments, wherein a first S segment is engineered to carry an ORF encoding GP in a position under control of a Pichinde virus 5′ UTR and an ORF encoding a first gene of interest in a position under control of a Pichinde virus 3′ UTR and a second S segment is engineered to carry an ORF encoding NP in a position under control of a Pichinde virus 5′ UTR and an ORF encoding a second gene of interest in a position under control of a Pichinde virus 3′ UTR.
Dependencies are inferred from the claim text.