Attenuation of human respiratory syncytial virus by genome scale codon-pair deoptimization

A recombinant polynucleotide comprising a recombinant nucleotide sequence encoding respiratory syncytial virus (RSV) proteins NS1, NS2, G, F, or L or a combination thereof,

• wherein the codon pair bias of each recombinant nucleotide sequence encoding the RSV protein is reduced by at least 0.05 compared to a wild type RSV subgroup A virus for a corresponding nucleotide sequence encoding the RSV protein,
• wherein a recombinant nucleotide sequence encoding RSV protein NS1 has about 75% to about 95% identity to the wild type RSV subgroup A virus for the corresponding nucleotide sequence encoding RSV protein NS1,
• wherein a recombinant nucleotide sequence encoding RSV protein NS2 has about 75% to about 95% identity to the wild type RSV subgroup A virus for the corresponding nucleotide sequence encoding RSV protein NS2,
• wherein a recombinant nucleotide sequence encoding RSV protein G has about 65% to about 85% identity to the wild type RSV subgroup A virus for the corresponding nucleotide sequence encoding RSV protein G,
• wherein a recombinant nucleotide sequence encoding RSV protein F has about 65% to about 85% identity to the wild type RSV subgroup A virus for the corresponding nucleotide sequence encoding RSV protein F,
• wherein a recombinant nucleotide sequence encoding RSV protein L has about 70% to about 90% identity to the wild type RSV subgroup A virus for the corresponding nucleotide sequence encoding RSV protein L,
• and
• wherein the recombinant nucleotide sequence encodes a RSV amino acid sequence that is the same as the corresponding wild type RSV subgroup A virus amino acid sequence, or a RSV amino acid sequence with up to four amino acid substitutions, additions or deletions compared to the corresponding wild type RSV subgroup A virus amino acid sequence.