Recombinant paramyxoviruses including a viral genome encoding a heterologous gene are provided. In several embodiments, the recombinant paramyxovirus is a recombinant parainfluenza virus, such as a recombinant PIV3 including a viral genome encoding a heterologous respiratory syncytial virus F ectodomain linked to the transmembrane domain and the cytoplasmic tail of the F protein from the PIV3. Nucleic acid molecules including the genome of a recombinant paramyxoviruses are also provided. The recombinant viruses may advantageously be used in vaccine formulations, such as for vaccines against parainfluenza virus and respiratory syncytial virus.

The present invention provides safe, stable, efficacious, and cost-effective vaccines based on viral expression vectors that include a parainfluenza virus 5 (PIV5) genome including a heterologous nucleotide sequence expressing a heterologous polypeptide.

The present invention includes the Paramyxovirus Parainfluenza Virus 5 (PIV5) as an oncolytic agent for treating various cancers, including, but not limited to breast cancer, lung cancer and melanoma. PIV5 oncolytic agents include both wild type PIV5 and various recombinant PIV5 constructs. Recombinant PIV5 constructs may include PIV5 lacking the conserved C-terminus of the V protein (PIV5V?C), PIV5 with mutations in the N-terminus of the V/P protein (PIV5CPI?), and PIV5 expressing MDA-7/IL-24 (rPIV5-MDA7), rPIV5-V/P-CPI?, rPIV5-CPI+, rPIV5-Rev, rPIV5-RL, rPIV5-P-S157A, rPIV5-P-S308A, rPIV5-L-A1981D, rPIV5-F-S443P, rPIV5-MDA7, rPIV5?SH-CPI?, or rPIV5?SH-Rev. Also included are methods of making and using such oncolytic agents and compositions including such oncolytic agents.

The present invention provides the complete genomic sequence of the epidemic mumps virus (MuV) strain MuV.sup.Iowa/US/06. Further, a reverse genetics system was constructed and used to rescue recombinant viral constructs that are attenuated compared to rMuV.sup.Iowa/US/06 and JL vaccine viruses. Such constructs include viral constructs lacking the open reading frame (ORF) of the SH gene (rMuVSH) and/or incapable of expressing the V protein (rMuVV).

The present invention includes the Paramyxovirus Parainfluenza Virus 5 (PIV5) as an oncolytic agent for treating various cancers, including, but not limited to breast cancer, lung cancer and melanoma. PIV5 oncolytic agents include both wild type PIV5 and various recombinant PIV5 constructs. Recombinant PIV5 constructs may include PIV5 lacking the conserved C-terminus of the V protein (PIV5V?C), PIV5 with mutations in the N-terminus of the V/P protein (PIV5CPI?), and PIV5 expressing MDA-7/IL-24 (rPIV5-MDA7), rPIV5-V/P-CPI?, rPIV5-CPI+, rPIV5-Rev, rPIV5-RL, rPIV5-P-S157A, rPIV5-P-S308A, rPIV5-L-A1981D, rPIV5-F-5443P, rPIV5-MDA7, rPIV5?SH-CPI?, or rPIV5?SH-Rev. Also included are methods of making and using such oncolytic agents and compositions including such oncolytic agents.

Recombinant paramyxoviruses including a viral genome encoding a heterologous gene are provided. In several embodiments, the recombinant paramyxovirus is a recombinant parainfluenza virus, such as a recombinant PIV3 including a viral genome encoding a heterologous respiratory syncytial virus F ectodomain linked to the transmembrane domain and the cytoplasmic tail of the F protein from the PIV3. Nucleic acid molecules including the genome of a recombinant paramyxoviruses are also provided. The recombinant viruses may advantageously be used in vaccine formulations, such as for vaccines against parainfluenza virus and respiratory syncytial virus.

A CVB viral expression vector comprising a PIV5 W3A viral genome that contains mutations at amino acid residue S157 or S156 in the P/V gene and a deletion of the small hydrophobic (SH) gene of the PIV5 W3A viral genome, wherein the amino acid substitution at amino acid residue S157 or S156 comprises a substitution of serine (S) to phenylalanine (F) or asparagine (N) and wherein the SH gene has a deletion of the SH open reading frame or a deletion of an entire SH gene transcript unit. The CVB viral expression vector wherein the vector expresses a heterologous polypeptide comprising a SARS-CoV-2 spike (S), and/or nucleocapsid (N) and/or membrane (M) proteins, RSV fusion protein (F) or other antigens.

Recombinant paramyxoviruses including a viral genome encoding a heterologous gene are provided. In several embodiments, the recombinant paramyxovirus is a recombinant parainfluenza virus, such as a recombinant PIV3 including a viral genome encoding a heterologous respiratory syncytial virus F ectodomain linked to the transmembrane domain and the cytoplasmic tail of the F protein from the PIV3. Nucleic acid molecules including the genome of a recombinant paramyxoviruses are also provided. The recombinant viruses may advantageously be used in vaccine formulations, such as for vaccines against parainfluenza virus and respiratory syncytial virus.

Recombinant paramyxoviruses including a viral genome encoding a heterologous gene are provided. In several embodiments, the recombinant paramyxovirus is a recombinant parainfluenza virus, such as a recombinant PIV3 including a viral genome encoding a heterologous respiratory syncytial virus F ectodomain linked to the transmembrane domain and the cytoplasmic tail of the F protein from the PIV3. Nucleic acid molecules including the genome of a recombinant paramyxoviruses are also provided. The recombinant viruses may advantageously be used in vaccine formulations, such as for vaccines against parainfluenza virus and respiratory syncytial virus.

Compositions, methods of use and methods of manufacture are provided for PIV5-based amplifying VLP (AVLP) that can deliver an expressible heterologous nucleotide sequence in target cells without producing progeny, and which demonstrate useful safety and therapeutic efficacy in multiple animal and human health applications, such as vaccination, gene therapy and cancer therapy.