Attenuation of human respiratory syncytial virus by genome scale codon-pair deoptimization
AssigneesThe United States of America, as represented by the Secretary, Department of Health and Human Services, The Research Foundation for The State University of New York
InventorsPeter L. Collins, Cyril Le Nouen, Linda G. Brock, Ursula J. Buchholz, Joshua Marc Dinapoli, Steffen Mueller, Eckard Wimmer
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Abstract
Described herein are RSV polynucleotide sequences that make use of multiple codons that are containing silent nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce a numerous synonymous codons into the genome. Due to the large number of defects involved, the attenuated viruses disclosed herein provide a means of producing attenuated, live vaccines against RSV.
Claims20
A recombinant polynucleotide comprising a recombinant nucleotide sequence encoding respiratory syncytial virus (RSV) proteins NS1, NS2, or both,
- wherein the codon pair bias of the recombinant nucleotide sequence encoding NS1 is reduced by at least 0.05 compared to a wildtype RSV for a corresponding nucleotide sequence encoding the RSV protein, or
- wherein the codon pair bias of the recombinant nucleotide sequence encoding NS2 is reduced by at least 0.05 compared to a wildtype RSV for a corresponding nucleotide sequence encoding the RSV protein, or
- both.
The recombinant virus of 14, wherein the recombinant genome or antigenome is modified to include a previously characterized RSV mutation or deletion.
Dependencies are inferred from the claim text.