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. Also disclosed herein are methods, compositions and cells for propagating the viral mutants, and methods, devices and compositions related to vaccination.

The present invention provides for parenterally administrable live attenuated influenza immune compositions. Methods of using parenterally administrable live attenuated influenza immune compositions to elicit an immune response, and particularly, a protective immune response are also provided.

The present invention includes antigenic fusion proteins, nucleic acids encoding the fusion proteins and methods of making and using the same, wherein the fusion protein comprises three or more different influenza A ectodomains of Matrix Protein 2 (M2e); one or more stem regions of an influenza A hemagglutinin 2 (HA2) protein; and optionally an anthrax antigen, wherein the fusion protein is immunogenic across strains.

The present application provides an attenuated orthomyxovirus-based (e.g., influenza A virus (IAV)-based) replicon vector, which optionally encodes a biological cargo, and in which the one or more envelope glycoprotein transcripts are engineered to comprise one or more miRNA Silencing Elements (MSEs) such that the one or more vector envelope glycoproteins are expressed in a first cell type or species, but are not expressed in a second cell type or species, wherein the introduction of the attenuated replicon vector into the second cell type or species results in a sustained production of the biological cargo in the absence of vector propagation and cell death and/or toxicity. In other aspects, the present application is directed to the attenuated replicon vector production and its use for sustained production of biological cargo in vivo and prevention and treatment of diseases.

Recombinant, chimeric porcine influenza viruses are disclosed that include hemagglutinin segments from more than one influenza virus subtype. Also described are methods of producing the recombinant influenza viruses, immunogenic compositions comprising the recombinant influenza viruses, methods of stimulating an immune response against influenza virus, and methods of treating and preventing influenza virus infection.

This invention provides an attenuated virus which comprises a modified viral genome containing nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce synonymous deoptimized codons into the genome. The instant attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the instant attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the instant attenuated virus.

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. Also disclosed herein are methods, compositions and cells for propagating the viral mutants, and methods, devices and compositions related to vaccination.

Engineered, replication-deficient influenza viruses that are infectious and stimulate broadly-cross protective immunity against multiple different influenza strains have been developed. Compositions and methods for providing protective immune responses against influenza are provided. The methods deliver compositions of intact, replication-deficient influenza viruses by intradermal administration in an amount effective to elicit or stimulate a cross-protective immune response to influenza viruses in the recipient following a single administration. Because the engineered influenza viruses are non-replicating, they are safe and effective in immunocompromised subjects. Methods for delivering co-stimulatory molecules, growth factors, adjuvants and/or cytokines together with the non-replicating influenza viruses are also provided.

The present invention provides for compositions comprising deoptimized influenza viruses and methods of using the composition for the treatment of cancer. Wherein treating a malignant tumor, comprises: administering a deoptimized influenza virus to a subject in need thereof, wherein an HA protein of the deoptimized influenza virus is encoded by a nucleic acid having a specified sequence.

Provided herein are flu hemagglutinin polypeptides, including chimeric influenza virus hemagglutinin polypeptides, and flu hemagglutinin polypeptides comprising modified glycosylation sites and non-naturally glycosylation sites, compositions comprising the same, vaccines comprising the same and methods of their use.