Disclosed herein are compositions and methods related to mutant viruses, and in particular, mutant influenza viruses. The mutant viruses disclosed herein include a mutant M2 sequence, and are useful in immunogenic compositions, e.g., as vaccines. The mutant viruses disclosed herein including a mutant M2 sequence are also useful to deliver antigens to a subject, e.g., to induce an immune response to the antigen. Also disclosed herein are methods, compositions and cells for propagating the viral mutants, and methods, devices and compositions related to vaccination.

The disclosure provides for an isolated recombinant influenza virus having at least one of: a PB2 viral segment encoding PB2 with residue at position 540 that is not asparagine or a residue at position 712 that is not glutamic acid, a PA viral segment encoding PA with a residue at position 180 that is not glutamine or a residue at position 200 that is not threonine, or a PB1 viral segment encoding PB1 with a residue at position 149 that is not valine, a residue at position 684 that is not glutamic acid or a residue at position 685 that is not aspartic acid, or any combination thereof, and methods of making and using the virus.

Described herein are modified RNA virus gene segments and nucleic acids encoding modified RNA virus gene segments. Also described herein are recombinant RNA viruses comprising modified RNA virus gene segments and the use of such recombinant RNA viruses for the prevention and treatment of disease.

The present invention relates to an mammalian non-pathogenic, highly-productive-in-embryonated-egg, heat-resistant, and attenuated clade 2.3.4.4c H5N6 recombinant influenza A virus, and a vaccine composition including the recombinant influenza virus and artificial H5 gene as active ingredients.

RNA virus vectors comprising a gene encoding the DNA-dependent activator of interferon-regulatory factors (DAI) protein, and optionally further comprising a gene encoding the receptor-interacting serine/threonine-protein kinase 3 (RIPK3) may be used therapeutically to induce cell death, as well as an inflammatory immune response, against tumors and virally-infected cells.

The invention provides a recombinant virus comprising an influenza viral backbone, wherein the influenza viral backbone comprises PB1, PB2, PA, NP, M, NS, HA, and NA gene segments, wherein at least one of the PB1, PB2, PA, NP, M, NS, HA, and NA gene segments comprises at least one nucleotide sequence that encodes one or more antigens. The invention provides a recombinant virus wherein the antigen is an immunogenic fragment of SARS-CoV-2 spike glycoprotein. The invention also provides a pharmaceutical formulation and a method of eliciting an immune response.

Disclosed are compositions and methods comprising one or more recombinant influenza viruses. Recombinant influenza viruses with mutated polymerases and/or rearranged genomes are disclosed. Constructs comprising different influenza nucleic acid sequences are also provided. Methods of inducing protecting immunity with the recombinant influenza viruses are disclosed. Also disclosed are methods of plasmid-free production of influenza virus comprising amplicons comprising one or more of influenza genes.

Engineered Influenza polynucleotides, viruses, vaccines, and methods of making and using the same are provided. More specifically, the present inventors have developed replication competent engineered influenza viruses having, for example, a modified segment 4 and/or segment 6 that include at least one additional polynucleotide encoding a heterologous polypeptide.

The invention provides a recombinant biologically contained influenza virus that is a PB2 knockout virus, e.g., one that is useful to generate a multivalent vaccine, and methods of making and using that virus.

Recombinant constructs, influenza viral genomes including the recombinant constructs, influenza viruses including the constructs, and vaccine formulations formed thereof for inducing or increasing an immune response against influenza virus are provided. The compositions typically include a nucleic acid having a nucleic acid sequence encoding IgA-inducing protein (IGIP) polypeptide that can positively regulate IgA expression operably linked to expression of a hemagglutinin or a neuraminidase. When the nucleic acid is expressed by recombinant influenza virus in infected cells, it preferably enhances IgA production against influenza virus. Live attenuated virus expressing IGIP, and methods of use thereof for treating and preventing influenza infections are also provided.