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.

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.

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.

Provided herein are engineered hMPV F proteins. In some aspects, the engineered F proteins exhibit enhanced conformational stability and/or antigenicity. Methods are also provided for use of the engineered F proteins as diagnostics, in screening platforms, and/or in vaccine compositions.

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.

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.

The present application generally relates to the development of live attenuated Pneumoviridae strains suitable for use as a vaccine. Particularly, human metapneumovirus (hMPV) M2-2 strains (rhMPV-E30M31 and rhMPV-E40L42D44) containing point mutations in a PDZ motif of M2-2, which results in a strain that is both attenuated and immunogenic and, notably, maintains the function of F and G proteins. These live attenuated hMPV strains should be suitable for use in a vaccine capable of providing protection against respiratory infection elicited by hMPV. Additionally, human respiratory syncytial virus (hRSV) strains containing point mutations in a PDZ motif of M2-2 should also be suitable for use as a vaccine capable of providing protection against respiratory infection elicited by hRSV. These Pneumoviridae strains should be useful in vaccines for use in humans and animals, e.g., companion animals and livestock, in treating or providing immunoprotection against respiratory infections.

The present invention relates to a vaccine composition for preventing and/or treating a respiratory system infection such as a human metapneumovirus infection of the respiratory system. This vaccine composition comprises one, two or more modified human metapneumovirus (hMPV) F proteins or variants thereof provided in a pre-fusion -fusion conformation form.

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 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.