Reported herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype in which the native positions of the NS1 and/or NS2 genes in the RSV genome are shifted to a higher position, that is at positions that are more distal to the promoter. The changes in the gene positions may be present in combination with mutations at other loci to achieve desired levels of attenuation and immunogenicity. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

Provided herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype that contain mutations in the M2-2 open reading frame that interfere with the expression of the M2-2 protein. The M2-2 mutations may be present in combination with mutations at other loci. Using methods described herein, combinations of mutations are provided to achieve desired levels of attenuation. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences of the described viruses, as well as methods for producing and using the viruses.

Provided herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype that contain mutations in the M2-2 open reading frame that interfere with the expression of the M2-2 protein. The M2-2 mutations may be present in combination with mutations at other loci. Using methods described herein, combinations of mutations are provided to achieve desired levels of attenuation. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences of the described viruses, as well as methods for producing and using the viruses.

Provided herein, in some embodiments, are vaccines (and vaccination methods) that include a ribonucleic acid (RNA) polynucleotide encoding a human metapneumovims (hMPV) F protein and a RNA polynucleotide encoding a human parainfluenza virus 3 (hPrV3) F protein.

Reported herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype in which the native positions of the NS1 and/or NS2 genes in the RSV genome are shifted to a higher position, that is at positions that are more distal to the promoter. The changes in the gene positions may be present in combination with mutations at other loci to achieve desired levels of attenuation and immunogenicity. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

Provided herein are recombinant respiratory syncytial viruses that contain mutations that make the disclosed viruses attractive vaccine candidates. The viruses disclosed contain attenuating mutations designed to have increased genetic and phenotypic stability. Desired combinations of these mutations can be made to achieve desired levels of attenuation. Exemplary vaccine candidates are described. Also provided are polynucleotides capable of encoding the described viruses, as wells as methods for producing the viruses and methods of use.

Methods for improving the drying yield and stability of RSV vaccines comprising a highly thermolabile enveloped live virus and/or one or more RSV protein subunits, are described. Methods for rapid drying of RSV formulations containing between 17.5% and 60% w/w of a non-polymeric sugar and using either conduction or radiation dominant drying mechanisms, are disclosed. The disclosed methods provide for; 1) a dried RSV formulation with improved stability profile; 2) faster drying; and 3) integration of dried RSV into a primary device (such as dual chamber cartridges, foil-pouch devices etc.), pre- as well as post-drying.

Reported herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype in which the native positions of the NS1 and/or NS2 genes in the RSV genome are shifted to a higher position, that is at positions that are more distal to the promoter. The changes in the gene positions may be present in combination with mutations at other loci to achieve desired levels of attenuation and immunogenicity. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

Embodiments disclosed herein provide compositions, methods, and uses for respiratory syncytial viruses (RSV) and immunogenic compositions thereof. Certain embodiments provide RSV having a mutated NS1 protein, where the mutation causes the uncoupling of the NS1 protein's replication and type I interferon (IFN) antagonist functions. In some embodiments, this uncoupling can produce virions capable of inducing a strong, long-lasting innate immune response while maintaining its ability to replicate in vitro. Also provided are methods for amplifying RSV in host cells, wherein amplified RSV has mutated NS1 protein in which the protein's replication and IFN antagonistic functions are uncoupled. In certain embodiments, the amplified RSV having mutated NS1 protein is formulated into immunogenic compositions, including vaccines. Other embodiments provide methods for inducing an effective immune response against RSV infection in a subject.

Provided herein are recombinant respiratory syncytial viruses that contain mutations that make the disclosed viruses attractive vaccine candidates. The viruses disclosed contain attenuating mutations designed to have increased genetic and phenotypic stability. Desired combinations of these mutations can be made to achieve desired levels of attenation. Exemplary vaccine candidates are described. Also provided are polynucleotides capable of encoding the described viruses, as wells as methods for producing the viruses and methods of use.