In one aspect, provided herein are recombinant neuraminidases comprising an ectodomain of influenza virus neuraminidase with amino acid substitutions or insertions of cysteines in the stalk domain to generate a more stable, tetrameric influenza virus neuraminidase. In specific embodiments, the influenza virus neuraminidase further comprises influenza virus neuraminidase transmembrane and cytoplasmic domains. In another aspect, provided herein are recombinant neuraminidase comprising a globular head domain of influenza virus neuraminidase and a tetramerization domain, wherein the recombinant neuraminidase lacks influenza virus neuraminidase stalk, transmembrane and cytoplasmic domains. In another aspect, provided herein are methods of immunizing against influenza virus using such recombinant neuraminidases or compositions thereof.

An engineered Newcastle Disease Virus (NDV) vector is provided. In particular, the present disclosure provides methods of treating or preventing a disease such as cancer, or an infectious disease, or methods for eliciting an immune response, with the engineered NDV vector. The engineered NDV vector provided herein is useful as an immunogenic composition, an oncolytic agent, or a vaccine.

Embodiments of immunogens comprising a recombinant Mumps (MuV) F ectodomain trimer stabilized in a prefusion conformation or a recombinant Measles (MeV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also provided are embodiments of immunogens comprising chimeric proteins comprising the recombinant MuV or MeV F ectodomain trimer and one or more MuV HN or MeV H ectodomains. Also disclosed are nucleic acids encoding the immunogens and methods of their production. Methods for inducing an immune response in a subject by administering a disclosed immunogen to the subject are also provided. In some embodiments, the immune response treats or inhibits MuV and/or MeV infection in a subject.

Disclosed are chimeric polypeptides based on viral membrane fusion proteins. More particularly, the present invention discloses chimeric polypeptides that comprise a virion surface exposed portion of a viral fusion protein and a heterologous structure-stabilizing moiety, and to complexes of those chimeric polypeptides. The present invention also discloses the use of these complexes in compositions and methods for eliciting an immune response to a fusion protein of an enveloped virus, or complex of the fusion protein, and/or for treating or preventing an enveloped virus infection. The present invention further discloses the use of the heterologous structure-stabilizing moiety for oligomerizing heterologous molecules of interest.

Disclosed herein are nanostructures and their use, where the nanostructures include a plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides selected from 153_dn5A, 153_dn5A.1 and I53_dn5A.2, or variants thereof; and a plurality of second assemblies, each second assembly comprising a plurality of identical second polypeptides being 153 dn5B or a variant thereof, 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.

Provided are modified virus-like particles (VLPs) of paramyxoviruses, compositions containing them, methods of using the VLPs for delivery of any particular protein of interest to any of a variety of cells, kits that contain expression vectors for making, using and detecting VLPs, and methods for screening for anti-viral compounds using the VLPs. The modified VLPs contain a contiguous recombinant polypeptide that contains i) all or a segment of a C-terminal domain of a paramyxovirus nucleocapsid protein and ii) a polypeptide sequence of a distinct protein. Non-covalent complexes of paramyxovirus M protein and fusion proteins that contain a C-terminal domain of a paramyxovirus nucleocapsid protein and a polypeptide sequence of a distinct protein are provided, as are non-covalent complexes of cells, and cell receptors, with modified VLPs.

The invention relates to RNA constructs encoding (i) at least one therapeutic biomolecule; and (ii) at least one innate inhibitor protein (IIP). The constructs are RNA replicons and saRNA molecules, and the invention includes genetic constructs or vectors encoding such RNA replicons. The invention extends to the use of such RNA constructs and replicons in therapy, for example in treating diseases and/or in vaccine delivery. The invention extends to pharmaceutical compositions comprising such RNA constructs, and methods and uses thereof.

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 nanostructures; 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.

Self-assembled protein nanoparticle (SAPN) are excellent antigen due to its ability to simultaneously present multiple epitopes to B cell and generate much stronger B cell receptor signaling than single epitope. Most of the SAPN are derived from capsid protein of virus or bacterial phage, which suffer from low particle stability, existing antibody against capsid protein and structural intolerant to peptide insertion. In this invention, we have created a SAPN using non-viral protein that is both thermal stable and tolerate to target peptide insertions. The assembling subunit of this SAPN is a fusion protein between two components: first, a polymerization module composed of an amphipathic helical peptide modified from M2 protein of type A influenza virus and second, a target peptide presentation module that composed of a superfolder green fluorescent protein (sfGFP) with a peptide insertion site on a specific loop of sfGFP. This particle is able to incorporate target peptide through genetic recombination and presented the target protein in the surface of nanoparticle to stimulate the production of high affinity antibody against target peptide without using adjuvant.

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 nanostructures; 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.