LIVE-ATTENUATED VIRUS AND METHODS OF PRODUCTION AND USE

摘要

Presented herein are live-attenuated viruses and methods of generating thereof from a parental virus through a plurality of nucleotide substitutions in the viral genome. The nucleotide substitutions result in a change in codon usage bias within codons of one or more protein encoding sequences and no change in amino acid sequences of the proteins. The live-attenuated viruses display unaltered replication in avian hosts for propagation, but attenuated replication in mammalian hosts, when compared to the replication of the parental virus. The live-attenuated viruses in a form of improved vaccines can be used to elicit protective immune responses.

主权项

1. A live-attenuated virus comprising a genome genetically engineered from a wild type virus to have mutated codons having an avian viral codon usage bias, the mutated codons having an avian viral codon usage bias present at conserved sites at the amino acid level and absent from genomic regions involving packaging or splicing, or overlapping reading frames encoding multiple proteins.