Recombinant vesiculoviruses and their uses
AssigneeYale University
InventorJohn K. Rose
Life of this patent
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Abstract
The invention provides recombinant replicable vesiculoviruses. The invention provides a method which, for the first time, successfully allows the production and recovery of replicable vesiculoviruses, as well as recombinant replicable vesiculoviruses, from cloned DNA, by a method comprising expression of the full-length positive-strand vesiculovirus antigenomic RNA in host cells. The recombinant vesiculoviruses do not cause serious pathology in humans, can be obtained in high titers, and have use as vaccines. The recombinant vesiculoviruses can also be inactivated for use as killed vaccines.
Claims58
A modified recombinant replicable vesiculovirus, comprising vesiculovirus N, P, and L proteins, and a replicable vesiculovirus genomic sense (−) RNA, in which said genomic sense (−) RNA, is modified by:
- (a) the insertion of a foreign RNA sequence into a nonessential portion of said replicable vesiculovirus genomic sense (−) RNA;
- or
- (b) the replacement of a nonessential portion of said replicable vesiculovirus genomic sense (−) RNA with a foreign RNA sequence,
- in which an RNA sequence complementary to said foreign RNA sequence encodes a peptide or protein that will induce an immune response to said peptide or protein when expressed in a suitable host infected with said modified recombinant replicable vesiculovirus.
A modified inactivated recombinant vesiculovirus that is the product of a method comprising inactivating a recombinant replicable vesiculovirus, said recombinant replicable vesiculovirus comprising vesiculovirus N, P, and L proteins, and a replicable vesiculovirus genomic sense (−) RNA, in which said genomic sense (−) RNA, is modified by:
- (a) the insertion of a foreign RNA sequence into a nonessential portion of said replicable vesiculovirus genomic sense (−) RNA;
- or
- (b) the replacement of a nonessential portion of said replicable vesiculovirus genomic sense (−) RNA with a foreign RNA sequence,
- in which an RNA sequence complementary to said foreign RNA sequence encodes a peptide or protein that will induce an immune response to said peptide or protein when expressed in a suitable host infected with said recombinant replicable vesiculovirus.
A pure, recombinant, replicating and infectious vesicular stomatitis virus (VSV) particle, comprising
- 1) a functional RNA dependent RNA polymerase (L);
- 2) a vesiculovirus phosphoprotein (P);
- 3) a vesiculovirus nucleocapsid (N);
- 4) vesiculovirus protein selected from the group consisting of glycoprotein (G) and matrix (M);
- 5) a 3′ non-coding RNA sequence;
- 6) a 3′ to 5′ RNA coding sequence, which encodes the vesiculovirus L, P, N, and vesiculovirus protein required for assembly of budded infectious particles and includes a heterologous gene (X), wherein said heterologous gene (X) is inserted at an intergenic junction;
- and
- 7) a 5′ non-coding RNA sequence, and
- wherein components 1 through 7 are from the same type of VSV.
Dependencies are inferred from the claim text.