FIELD: biotechnology.
SUBSTANCE: recombinant respiratory-syncytial virus (hereinafter – RSV) is described for inducing an immune response to RSV, attenuated by one or several modifications to a recombinant RSV genome, where one or more modifications include: (a) deletion in M2-2 open reading frame (hereinafter – ORF), corresponding to deletion of 241 nucleotides at positions 8189-8429 of SEQ ID NO: 1, in combination with nucleotide mutations at positions corresponding to T8161, T8167 and T8179 of SEQ ID NO: 1 (“ΔM2-2”); (b) deletion in M2-2 ORF, corresponding to deletion of 234 nucleotides at positions 8203-8436 of SEQ ID NO:1, in combination with nucleotide mutations at positions corresponding to 8198A and 8200G of SEQ ID NO:1 (“ΔM2-2-AclI”); or (c) deletion in M2-2 ORF, corresponding to deletion of 234 nucleotides at positions 8203-8436 of SEQ ID NO: 1, in combination with nucleotide mutations at positions corresponding to 8198A and 8199G of SEQ ID NO: 1 (“ΔM2-2-HindIII”), where the recombinant RSV genome is D46 genome attenuated by one or several modifications. A recombinant respiratory-syncytial virus (RSV) is also described for inducing an immune response to RSV, attenuated by one or several modifications to the recombinant RSV genome, where one or more modifications include: deletion in M2-2 ORF, corresponding to deletion of 234 nucleotides at positions 8203-8436 of SEQ ID NO: 1, in combination with nucleotide mutations at positions corresponding to 8198A and 8199G of SEQ ID NO: 1 (“ΔM2-2-HindIII”), and deletion of 112 nucleotides, corresponding to positions 4499-4610 of SEQ ID NO:1, in combination with nucleotide mutations at positions corresponding to C4489T, C4492T, A4495T, A4497G and G4498A of SEQ ID NO: 1 (“6120”). Corresponding polynucleotides, vectors and cells are presented. In addition, a vaccine containing the specified virus is presented. A method for producing the specified virus is described. The invention relates to combinations of mutations using methods described in the present invention to achieve desired levels of attenuation.
EFFECT: recombinant RSV strains described in the present invention are suitable for use as live attenuated RSV vaccines.
46 cl, 16 dwg, 24 tbl, 9 ex
