Vaccine against bovine leukemia virus
AssigneesUniversite De Liege, Instituto Nacional De Tecnologia Agropecuaria
InventorsLuc Willems, Karina Trono
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Abstract
The invention relates to recombinant bovine leukemia viruses that have an attenuated phenotype and comprise a combination of at least two specific mutations. The invention also provides recombinant nucleic acids encoding such viruses, vectors comprising such nucleic acids, and host cells comprising such nucleic acids or vectors. The recombinant attenuated BLV viruses, recombinant nucleic acids, vectors and host cells allow for the preparation of improved vaccines, in particular vaccines suitable for the prophylactic treatment of BLV-associated diseases in subjects. The invention further provides methods for treating BLV-associated diseases in subjects and pharmaceutical compositions suitable for use in these methods.
Claims47
A recombinant attenuated bovine leukemia virus (BLV) characterised in that the virus comprises:
- a mutation in the nucleic acid sequence encoding the most N-terminal YXXL signalling motif of the cytoplasmic domain of the transmembrane subunit (TM) of the envelope protein, said mutation disrupting the signal transduction activity of the motif,
- a mutation in G4 restricting the propagation of the BLV in vivo, and
- a mutation in R3 restricting the propagation of the BLV in vivo.
-5. (canceled)
The recombinant attenuated BLV according to claim 2, wherein the mutation in the X region of the BLV nucleic acid sequence abolishing the production of at least one or preferably all microRNA encoded by said X region is a deletion of at least a portion of the region of the BLV nucleic acid sequence between the stop codon of TM and the splice acceptor site of intron 2 of R3, such as between the stop codon of TM and about 50 nucleotides upstream of the intron 2-exon 3 boundary of R3, for example wherein the 5′ boundary of the deletion is located between about 1 and about 11 nucleotides downstream of the stop codon of TM and the 3′ boundary of the deletion is located between about 92 and about 72 nucleotides upstream of the intron 2-exon 3 boundary of R3.
The recombinant attenuated BLV according to claim 2, wherein the mutation in G4 restricting the propagation of the BLV in vivo and the mutation in R3 restricting the propagation of the BLV in vivo and the mutation in the X region of the BLV nucleic acid sequence abolishing the production of at least one or preferably all microRNA encoded by said X region are a deletion of at least a portion of the region of the BLV nucleic acid sequence between the stop codon of TM and the splice acceptor site of intron 2 of Tax/Rex, whereby the splice acceptor site of intron 2 of R3 and the splice acceptor site of intron 1 of G4 are deleted, for example wherein the 5′ boundary of the deletion is located between about 1 and about 11 nucleotides downstream of the stop codon of TM and the 3′ boundary of the deletion is located between about 55 and about 35 nucleotides upstream of the intron 2-exon 3 boundary of Tax/Rex.
(canceled)
The recombinant attenuated BLV encoded by the plasmid as deposited under the Budapest Treaty with the Belgian Coordinated Collections of Microorganisms BCCM™/LMBP Collection under accession number LMBP 8166 on Feb. 5, 2013.
The plasmid as deposited under the Budapest Treaty with the Belgian Coordinated Collections of Microorganisms BCCM™/LMBP Collection under accession number LMBP 8166 on Feb. 5, 2013.
A recombinant nucleic acid encoding a recombinant attenuated BLV, wherein the recombinant nucleic acid comprises, consists essentially of or consists of the insert of the plasmid as deposited under the Budapest Treaty with the Belgian Coordinated Collections of Microorganisms BCCM™/LMBP Collection under accession number LMBP 8166 on Feb. 5, 2013.
(canceled)
Dependencies are inferred from the claim text.