The present invention relates to the production of modified influenza viral proteins in plants. More specifically, the present invention relates to producing and increasing influenza virus-like particle (VLP) production in plants, wherein the VLPs comprise the modified influenza viral proteins, such as modified influenza hemagglutinin (HA). The HA protein may comprising an amino acid sequence comprising at least one substitution when compared to a corresponding wildtype amino acid sequence. Further provided are nucleic acid encoding the modified HA protein. Furthermore methods of producing an influenza virus like particle (VLP) and methods of increasing yield of production of an influenza virus like particle (VLP) in a plant, portion of a plant, or a plant cell, are also provided.

This disclosure describes a system for generating influenza virus or influenza virus proteins, methods of making that system, and methods of using that system.

A method for adapting an influenza virus to Vero cells is provided. The method comprises infecting Vero cells with the influenza virus, cultivating the infected Vero cells, harvesting influenza viruses of each passage, wherein infectious dose of the influenza viruses of one passage is greater than or equal to infectious dose of the influenza viruses of a previous passage. The present disclosure also relates to a composition. Said composition comprises polyriboinosinic acid-polyribocytidylic acid, at least one antibiotic or polyamide compound, at least one positive ion, influenza viruses and/or influenza antigens, wherein said influenza viruses and/or influenza antigens are acquired from Vero cell adapted influenza viruses.

An isolated recombinant influenza virus is provided having PA, PB1, PB2, NP, NS, M, NA and HA viral segments, wherein the PB1 viral segment encodes a PB1 with a residue other than isoleucine at position 711 or the M viral segment encodes a M1 with a residue other than methionine at position 128, wherein the recombinant influenza virus has enhanced replication relative to a corresponding influenza virus having a PB1 viral segment that encodes a PB1 with an isoleucine at position 711 or having a M viral segment that encodes a M1 with methionine at position 128, as well as methods of making and using the 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. 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.

Disclosed are compositions and methods for increasing influenza virus production.

Provided are compounds that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided.

The present invention refers to a process for purifying virus particles from cell culture, comprising the steps of subjecting the cell culture to centrifugation to get a supernatant fraction of virus particles, incubating said fraction with a nuclease, diluting the fraction with low conductivity buffer, subjecting said diluted fraction to a SO3 chromatography step, performing a washing step with low conductivity buffer, and eluting virus particles.

The invention provides a composition useful to prepare high titer influenza viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, and genes from vaccine seed virus isolates which include a HA gene segment with a HA2 sequence encoding a HA2 that confers enhanced growth in cells in culture, such as Vero cells.

Compositions and methods to prepare influenza virus-like particles (VLPs) are provided.