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.

An isolated expression enhancer active in a plant, portion of a plant or plant cell, the expression enhancer is provided. The isolated expression enhancer may be selected from the group consisting of nbEPI42 (SEQ ID NO:1); nbSNS46 (SEQ ID NO:2); nbCSY65 (SEQ ID NO:3); nbHEL40 (SEQ ID NO:4); and nbSEP44 (SEQ ID NO:5). Methods for using the isolated expression enhancer are also provided.

Various recombinant yeast suitable for use in oral vaccination, vaccine compositions, food compositions, methods of vaccinating an animal, and related methods, kits, and nucleic acid molecules are described.

A method of producing a virus like particle (VLP) in a plant comprising modified H3 hemagglutinin is provided. The method comprises introducing a nucleic acid comprising a regulatory region active in the plant and operatively linked to a nucleotide sequence encoding a modified influenza hemagglutinin (HA) protein into the plant, or portion of the plant, the modified HA protein comprises a modified proteolytic loop. Followed by incubating the plant or portion of the plant under conditions that permit the expression of the nucleic acids, thereby producing the VLP. The modified proteolytic loop may comprise one or more protease cleavage sites exhibiting reduced or abolished cleavage by a protease. Also described is a virus like particle (VLP) produced by the method, and plants expressing the VLP. The virus like particle (VLP) may comprise plant-specific N-glycans, or modified N-glycans.

The present invention provides, among other things, a novel and improved method for generating “mosaic” influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered H1N1 influenza hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple H1N1 viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.

Provided is a method for efficiently proliferating an influenza virus serving as a material for vaccine in a host.

A method for proliferating an influenza virus in a host, comprising a step of inhibiting transfer of Bax in a host cell to the inner mitochondrial membrane.

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

The present disclosure is directed to oral vaccine dosage forms and processes for producing the oral vaccine dosage forms. The dosage forms include lipid-based vesicles (e.g., virosomes, liposomes) harboring an immunogenic amount of at least one vaccinal target molecule, with or without adjuvant. Specifically, Applicants discovered a combination of the composition of the liquid virosome concentrates, the composition of the base matrix for the solid dosage form formulation (excluding the virosome concentrate), and the manufacturing conditions for the dosage forms that can produce a freeze dried sublingual dosage form having physical robustness, particle and antigen integrity and stability.

The present invention relates to the production of modified influenza vial 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 H A 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 H A 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.

The invention relates to an active ingredient which is a live attenuated recombinant measles virus expressing influenza A virus antigen(s) and to its use in the elicitation of immunity, in particular protective immunity and advantageously broad-spectrum protective immunity against influenza A virus. In particular, the influenza A virus is selected among epidemic seasonal viruses and/or endemic viruses circulating in the human population and advantageously encompasses a pandemic virus such as H1N1v.