Recombinant respiratory syncytial virus (RSV) are provided in which
expression of the second translational open reading frame encoded by the
M2 gene (M2ORF2) is reduced or ablated to yield novel RSV vaccine
candidates. Expression of M2 ORF2 is reduced or ablated by modifying a
recombinant RSV genome or antigenome to incorporate a frame shift
mutation, or one or more stop codons in M2 ORF2. Alternatively, M2 ORF2
is deleted in whole or in part to render the M2-2 protein partially or
entirely non-functional or to disrupt its expression altogether. M2 ORF2
deletion and knock out mutants possess highly desirable phenotypic
characteristics for vaccine development. These changes specify one or
more desired phenotypic changes in the resulting virus or subviral
particle. Vaccine candidates are generated that show a change in mRNA
transcription, genomic or antigenomic RNA replication, viral growth
characteristics, viral antigen expression, viral plaque size, and/or a
change in cytopathogenicity. In addition, M2-2 knock out or deletion
virus exhibits increased levels of synthesis of viral proteins in cell
culture, providing an enriched source of viral antigen or protein for
purification and use as a noninfectious subunit vaccine.