The invention relates to the field of virology. The invention provides an isolated essentially mammalian negative-sense single-stranded RNA virus (MPV) within the subfamily Pneumovirinae of the family Paramyxoviridae and identifiable as phylogenetically corresponding to the genus Metapneumovirus and components thereof.

Metapneumovirus (MPV) F proteins stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the MPV F proteins and/or nucleic acid molecules can be used to generate an immune response to MPV in a subject. In additional embodiments, the therapeutically effective amount of the MPV F ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing MPV infection.

The current disclosure relates to methods, compositions and kits for detecting modified adenosine in a target RNA molecule. Aspects relate to a method for detecting modified adenosine in a target ribonucleic acid (RNA) comprising contacting the target RNA with an adenosine deaminase enzyme (adenosine deaminase, RNA-specific) to generate a target RNA with deaminated adenosines and sequencing the target RNA with deaminated adenosines; wherein the modified adenosine is detected when the nucleotide sequence includes adenosine within a m6A motif.

Provided is an isolated mammalian negative strand RNA virus, metapneumovirus (MPV), within the sub-family Pneumoviridae, of the family Paramyxoviridae. Also provided are isolated mammalian negative strand RNA viruses identifiable as phylogenetically corresponding or relating to the genus Metapneumovirus and components thereof. In particular, provided is a mammalian MPV, subgroups and variants thereof. Also provided are genomic nucleotide sequences of different isolates of mammalian MPV, in particular, human MPV. Disclosed is the use of the sequence information of different isolates of mammalian MPV for diagnostic and therapeutic methods. Provided are nucleotide sequences encoding the genome of an MPV or a portion thereof, including both mammalian and avian MPV. Further described are chimeric or recombinant viruses encoded by the nucleotide sequences and chimeric and recombinant mammalian MPV that comprise one or more non-native or heterologous sequences. Also provided are vaccine formulations comprising mammalian or avian MPV, including recombinant and chimeric forms thereof. The vaccine preparations encompass multivalent vaccines, including bivalent and trivalent vaccine preparations.

Provided herein are a respiratory syncytial virus (RSV) vaccine composition including a messenger ribonucleic acid (mRNA) including an open reading frame (ORF) encoding RSV mutant F B strain protein, and optionally a mRNA including an ORF encoding RSV mutant F A strain protein, and a method of inducing immune response against RSV by administering an effective amount of the RSV vaccine composition to a subject in need thereof. Provided herein are also a respiratory syncytial virus (RSV) and human metapneumovirus virus (hMPV) vaccine composition including a mRNA including an ORF encoding RSV mutant F A strain protein, a mRNA including an ORF encoding RSV mutant F B strain protein, and a mRNA including an ORF encoding hMPV F protein, and a method of inducing immune response against RSV and hMPV by administering an effective amount of the RSV and hMPV vaccine composition to a subject in need thereof.

The invention relates to the field of virology. The invention provides an isolated essentially mammalian negative-sense single-stranded RNA virus (MPV) within the subfamily Pneumovirinae of the family Paramyxoviridae and identifiable as phylogenetically corresponding to the genus Metapneumovirus and components thereof.

Provided is an isolated mammalian negative strand RNA virus, metapneumovirus (MPV), within the sub-family Pneumoviridae, of the family Paramyxoviridae. Also provided are isolated mammalian negative strand RNA viruses identifiable as phylogenetically corresponding or relating to the genus Metapneumovirus and components thereof. In particular, provided is a mammalian MPV, subgroups and variants thereof. Also provided are genomic nucleotide sequences of different isolates of mammalian MPV, in particular, human MPV. Disclosed is the use of the sequence information of different isolates of mammalian MPV for diagnostic and therapeutic methods. Provided are nucleotide sequences encoding the genome of an MPV or a portion thereof, including both mammalian and avian MPV. Further described are chimeric or recombinant viruses encoded by the nucleotide sequences and chimeric and recombinant mammalian MPV that comprise one or more non-native or heterologous sequences. Also provided are vaccine formulations comprising mammalian or avian MPV, including recombinant and chimeric forms thereof. The vaccine preparations encompass multivalent vaccines, including bivalent and trivalent vaccine preparations.

Disclosed herein are nanostructures and their use, where the nanostructures include (a) a plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides; (b) a plurality of second assemblies, each second assembly comprising a plurality of identical second polypeptides, wherein the second polypeptide differs from the first polypeptide; wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form a nanostructure; and wherein the nanostructure displays multiple copies of one or more paramyxovirus and/or pneumovirus F proteins or antigenic fragments thereof, on an exterior of the nanostructure.

Chimeric polypeptides, chimeric fusion proteins, immunogenic compositions, and methods of use thereof for pan-pneumovirus vaccination are provided. The chimeric polypeptides typically include immunodominant epitopes of the fusion protein of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), and preferably include one or more of antigenic sites , V, and II of RSV, and III, IV, and DS7 of hMPV. The chimeric polypeptides can be utilized as the antigenic domain in chimeric fusion proteins include one or more additional domains such as a signal peptide sequence, a trimerization domain, a cleavage site, a purification tag or report sequence, and one or more linker sequences. Nucleic acids encoding the chimeric polypeptides and chimeric fusion proteins are also provided, as are recombinant viruses having the same. Pharmaceutical compositions including one or more of the foregoing compositions, and methods of there use for immunizing subjects against RSV and hMPV are also provided.

The present invention relates to a viral strain derived from the human metapneumovirus (hMPV) strain having a genome sequence represented by sequence SEQ ID NO. 1, wherein said genome sequence comprises the following genetic modifications: (i) inactivation of the endogenous gene coding for the SH protein and/or for the G protein, and (ii) presence of an exogenous nucleotide sequence coding for at least one extracellular domain of the F protein of the human respiratory syncytial virus (hRSV), said domain being wild-type or mutated.