Recombinant Rift Valley fever (RVF) viruses and methods of use
AssigneeThe United States of America as represented by the Secretary of the Department of Health and Human Services, Centers for Disease Control and Prevention
InventorsBrian H. Bird, Cesar G. Albarino, Stuart T. Nichol, Thomas G. Ksiazek
Life of this patent
Estimating the term…
Abstract
Described herein are recombinant RVF viruses comprising deletions in one or more viral virulence genes, such as NSs and NSm. The recombinant RVF viruses, generated using a plasmid-based reverse genetics system, can be used as vaccines to prevent infection of RVF virus in livestock and humans. As described herein, the recombinant RVF viruses grow to high titers, provide protective immunity following a single injection and allow for the differentiation between vaccinated animals and animals infected with wild-type RVF virus.
Claims25
A collection of plasmids comprising:
- (i) a plasmid encoding a full-length anti-genomic copy of the L segment of RVF virus;
- (ii) a plasmid encoding a full-length anti-genomic copy of the M segment of RVF virus, or an anti-genomic copy of the M segment of RVF virus comprising a complete deletion of the NSm ORF;
- and
- (iii) a plasmid encoding an anti-genomic copy of the S segment of RVF virus, wherein the S segment comprises a complete deletion of the NSs ORF,
- wherein the nucleotide sequence of the L segment plasmid is at least 95% identical to the nucleotide sequence of SEQ ID NO:
- 13, the nucleotide sequence of the M segment plasmid is at least 95% identical to the nucleotide sequence of SEQ ID NO:
- 12 or SEQ ID NO:
- 15, or the nucleotide sequence of the S segment plasmid is at least 95% identical to the nucleotide sequence of SEQ ID NO:
- 14.
A recombinant RVF virus, wherein the genome of the recombinant RVF virus comprises a full-length L segment, a full-length M segment and a full-length S segment, wherein the S segment encodes a NS s-reporter gene fusion protein.
A reverse genetics system for producing recombinant RVF virus consisting of three plasmids, wherein a first plasmid encodes an anti-genomic copy of a S segment, a second plasmid encodes an anti-genomic copy of a M segment and a third plasmid encodes an anti-genomic copy of a L segment of RVF virus, and wherein each plasmid comprises a T7 promoter and a hepatitis delta virus ribozyme,
- wherein the nucleotide sequence of the S segment plasmid is at least 95% identical to the nucleotide sequence of SEQ ID NO:
- 11 or SEQ ID NO:
- 14, the nucleotide sequence of the M segment plasmid is at least 95% identical to the nucleotide sequence of SEQ ID NO:
- 12 or SEQ ID NO:
- 15, or the nucleotide sequence of the L segment plasmid is at least 95% identical to the nucleotide sequence of SEQ ID NO:
- 13.
Dependencies are inferred from the claim text.