Abstract: The present invention concerns methods and means for identifying, producing, and engineering neutralizing molecules against influenza A viruses, and to the neutralizing molecules produced. In particular, the invention concerns neutralizing molecules against various influenza A virus subtypes, including neutralizing antibodies against H5 and/or H3 and/or H1, such as, for example all of H1, H3, and H5 subtypes, and methods and means for making such molecules.

Abstract: The present invention provides a vaccine composition for transnasal mucous membrane administration, which contains an influenza virus antigen, polyriboinosinic polyribocytidylic acid (poly (I:C)) or a derivative thereof and a carboxyvinyl polymer. The present invention also provides a prophylactic method of influenza, including a step of administering the vaccine composition at least once to the nasal mucosa of a subject in need thereof.

Abstract: Influenza vaccines include hemagglutinin from at least one influenza A virus strain and at least one influenza B virus strain. They also include an oil-in-water emulsion adjuvant with submicron oil droplets, comprising squalene. In some embodiments the hemagglutinin concentration is >12 ?g/ml per strain. In some embodiments the squalene concentration is <19 mg/ml. In some embodiments the vaccine is mercury-free. In some embodiments the vaccine has a unit dose volume between 0.2-0.3 mL. In some embodiments the squalene concentration is 9.75 mg/mL or 4.88 mg/mL. In some embodiments the vaccine includes antigens from two influenza A virus strains and two influenza B virus strains.

Abstract: Disclosed herein is the finding that baculovirus display of multiple influenza virus hemagglutinin (HA) proteins elicits broadly reactive immune responses against influenza. Thus provided herein are recombinant baculovirus vectors having a first, second, third and fourth nucleic acid sequence, each encoding an influenza hemagglutinin (HA) fusion protein. The first, second, third and fourth nucleic acid sequences each encode an influenza HA with a different amino acid sequence. Also provided are recombinant baculoviruses displaying a first, second, third and fourth influenza virus HA fusion protein in the baculovirus envelope, wherein each HA fusion protein comprises a different HA amino acid sequence. Tetravalent influenza virus vaccines comprising the recombinant baculoviruses disclosed herein are further provided. In addition, methods of immunizing a subject against influenza virus using the tetravalent influenza virus vaccines are provided.

Abstract: A method of purifying a virus, or a viral antigen thereof, from a culture of infected cells comprising at least the steps of: (a) collecting the virus-containing cell culture medium, and (b) purifying the virus, wherein at least one homogenization step is implemented during the purification to obtain a virus homogenate.

Abstract: The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to antigens and vaccines useful in prevention of infection by influenza virus. Provided are recombinant protein antigens, compositions, and methods for the production and use of such antigens and vaccine compositions.

Abstract: A vaccine for the treatment or prevention of a disease in a subject, wherein said disease is associated with an avian influenza virus, and wherein said vaccine comprises an expression vector comprising a nucleic acid encoding a hemagglutinin peptide, such that in use said hemagglutinin peptide is expressed by said expression vector in said subject.

Abstract: An influenza vaccine is administered by a multi-dose regimen, in which (i) a first dose is administered with an adjuvant and (ii) a later dose is administered either without an adjuvant or with a different adjuvant. Thus the invention provides the benefits of a two-dose regimen without also doubling the supply need for a given adjuvant.

Abstract: An influenza vaccine adjuvanted with a sub-micron oil-in-water emulsion elicits significantly higher immune responses in human pediatric populations. Compared to an existing unadjuvanted pediatric influenza vaccine, the adjuvanted vaccines provided herein can induce in children a longer persistence of high serum antibody titers and also longer seroconversion and seroprotection. The improvement in immune responses is seen for both influenza A virus and influenza B virus strains, but it is particularly marked for influenza B virus. Moreover, while the existing vaccine provides poor immunity in children after a single dose, the adjuvanted vaccine provides high seroprotection rates against the influenza A virus H3N2 subtype even after a single dose. Furthermore, the adjuvanted vaccine offers significantly better seroprotection against mismatched strains of influenza A virus.

Abstract: The disclosure relates at least in part to embodiments of compositions and methods including vaccines for protection against multiple serologically distinct strains of influenza virus. This disclosure provides significant advances and addresses important needs in the influenza vaccine field.

Abstract: The subject invention pertains to isolated influenza virus that is capable of infecting canids and causing respiratory disease in the canid. The subject invention also pertains to compositions and methods for inducing an immune response against an influenza virus of the present invention. The subject invention also pertains to compositions and methods for identifying a virus of the invention and diagnosing infection of an animal with a virus of the invention.

Abstract: The present invention discloses and claims virus like particles (VLPs) that express and/or contains seasonal influenza virus proteins, avian influenza virus proteins and/or influenza virus proteins from viruses with pandemic potential. The invention includes vector constructs comprising said proteins, cells comprising said constructs, formulations and vaccines comprising VLPs of the inventions. The invention also includes methods of making and administrating VLPs to vertebrates, including methods of inducing substantial immunity to either seasonal and avian influenza, or at least one symptom thereof.

Abstract: Pharmaceutical and vaccine compositions comprise recombinant hemagglutinin from a pre-pandemic or pandemic influenza virus and an adjuvant comprising GLA. A particularly relevant pre-pandemic influenza virus is H5N1. Kits and methods of using the compositions are also provided.

Abstract: A vaccine composition and method which is effective in preventing or ameliorating Avian Influenza Virus infection is set forth herein. The vaccine contains at least two inactivated strains of avian influenza virus, wherein the combined haemoagglutinin (HA) total is at least about 200 HA/dose of the vaccine composition, and wherein each of the strains presents at least about 128 HA/dose, and further wherein one of the strains has the same HA subtype as that of a challenge virus, and wherein at least one of the strains has a different NA subtype than the challenge virus.

Abstract: The present application pertains to a composition, comprising (a) amphipathic peptides; (b) lipids and (c) at least one immunogenic species. Respective compositions are suitable for immunogenic species transport and delivery, for example for systemic or local delivery to a mammal. Also provided are pharmaceutical compositions, comprising respective compositions. Methods of forming the foregoing are also provided.

Abstract: This disclosure is directed, inter alia, to polynucleotides, polypeptides, vectors, cells and compositions comprising the same, and their use in affecting viral pathogenesis, in particular for influenza viral infection.

Abstract: The present invention relates to a vaccine composition comprising: —at least one prophylactically active agent against influenza, and —at least one adjuvant, said adjuvant being a derivative of a galactosylceramide, for use in the treatment of influenza.

Abstract: Methods of delivering a cargo moiety to a cell is provided according to embodiments of the present invention which includes contacting a cell expressing sialoadhesin with a conjugate including a sialoadhesin binding moiety and a cargo moiety. The sialoadhesin binding moiety binds to the sialoadhesin expressed by the cell and is internalized along with the cargo, delivering the cargo moiety to the cell. Particular methods provided by the present invention include induction or enhancement of sialoadhesin expression in a cell which naturally produces little or no sialoadhesin. Induction or enhancement of sialoadhesin expression includes transfection of a sialoadhesin expression construct and/or administration of an agent effective to induce or enhance sialoadhesin expression. Methods and compositions for stimulating an immune response in a subject are detailed. Particular methods and compositions for stimulating an immune response to a virus are provided by the present invention.

Abstract: The subject invention pertains to influenza vaccines and particularly avian influenza vaccines (AIV). The invention includes methods for preparing transgenic plant cells to express know HA1 polypeptides having specified homologies that are used to prepare vaccine compositions and methods for inducing protective immunity in an individual, animal, mammal or human.

Abstract: A method for synthesizing influenza virus-like particles (VLPs) within a plant or a portion of a plant is provided. The method involves expression of a novel influenza HA protein in plants and its purification The invention is also directed towards a VLP comprising influenza HA protein and plants lipids. The invention is also directed to a nucleic acid encoding improved influenza HA as well as vectors. The VLPs may be used to formulate influenza vaccines, or may be used to enrich existing vaccines.

Abstract: The present invention aims to provide a method which enables efficient removal of impurities such as the host proteins from an influenza virus culture liquid by a simple operation, allowing separation and purification of an influenza virus antigen. The method of the present invention for producing a purified influenza virus antigen comprises the step of treating a sample containing an influenza virus with a surfactant, the step of bringing the sample after the treatment into contact with hydroxyapatite in the presence of the surfactant, and the step of recovering a hydroxyapatite-non-adsorbed fraction.

Abstract: This disclosure is directed, inter alia, to polynucleotides, polypeptides, vectors, cells and compositions comprising the same, and their use in affecting viral pathogenesis, in particular for influenza viral infection.

Abstract: Polypeptides, polynucleotides, methods, compositions, and vaccines comprising (avian pandemic) influenza hemagglutinin and neuraminidase variants are provided.

Abstract: A method of stimulating an immune response in a subject including administering a micrometer-sized particle coupled with an antigen to the subject, wherein increasing the aspect ratio of the micrometer-sized particle increases the immune response. A method of stimulating an immune response in a subject including administering to the subject a plurality of particles, wherein each particle is coupled with an immuno stimulating agent and a protein. A vaccine particle composition including a plurality of particles configured to release a first protein at a first rate and a second protein at a second rate and configured to provide priming and boosting capability in a single dose.

Abstract: Means and methods for producing mammalian viruses, the method comprising infecting a culture of immortalized human cells with a virus, incubating the culture infected with virus to propagate the virus under conditions that permit growth of the virus, and to form a virus-containing medium, and removing the virus-containing medium. The viruses can be harvested and be used for the production of vaccines. Advantages include that human cells of the present invention can be cultured under defined serum-free conditions and the cells show improved capability for propagating virus. Methods are provided for producing, in cultured human cells, influenza virus and vaccines derived thereof. This method eliminates the necessity of using whole chicken embryos for the production of Influenza vaccines. The method also provides for the continuous or batch-wise removal of culture media. As such, the present invention allows the large-scale continuous production of viruses to a high titer.

Abstract: Antigen and adjuvant components of an adjuvanted influenza vaccine are not mixed during manufacture, but are provided as separate components for extemporaneous mixing at the time of use, for example as a kit comprising (i) an antigen component, comprising an influenza virus antigen; and (ii) an adjuvant component, comprising an aluminium salt.

Abstract: Bacterial immunity proteins are utilized to increase immune response to an antigen of interest.

Abstract: The present invention relates to influenza vaccine formulations and vaccination regimes for immunizing against influenza disease. In particular the invention relates to vaccine formulations comprising an oil-in-water emulsion adjuvant and optionally 3D-MPL, their use in medicine, in particular their use in augmenting immune responses to influenza antigens, and to methods of preparation, wherein the oil in water emulsion comprises a sterol, a metabolizable oil and an emulsifying agent. The present invention also provides for new prime-boost vaccination regimes for immunizing humans against influenza disease, and in particular for ensuring and ameliorating the immune response to the booster administration, in which a first influenza virus vaccine is administered in the presence of an adjuvant.

Abstract: Compositions comprise a flagellin component that is at least a portion of a flagellin, wherein the flagellin component includes at least one cysteine residue and whereby the flagellin component activates a Toll-like Receptor 5. Compositions can further include an antigen, such as an influenza antigen. The compositions are used to stimulate an immune response and a protective immune response in a subject.

Abstract: Described herein are compositions that include a selected antigen, a TLR4 ligand and a TLR7/TLR8 ligand, wherein the antigen and TLR ligands are encapsulated in nanoparticles. Co-administration of both a TLR4 ligand and a TLR7/TLR8 ligand results in the synergistic induction of humor and cellular immunity as evidenced by an increase in pro-inflammatory cytokine production, an increase in the number of CD8+ T effector and T memory cells, an increase in titer of antigen-specific antibodies, an increase in antibody affinity, an increase in the proliferation of naïve B cells and/or a significant enhancement in the persistence of antibody and T cell responses. The compositions and methods provided herein can be used to stimulate an immune response such as an immune response to a pathogen or a tumor.

Abstract: The immunogenicity of the influenza virus hemagglutinin (HA) molecule may be increased by substitutions of amino acids in the HA sequence. The substitution of specific HA residues, such as asparagine at position 223 of H5 HA, increase the sensitivity of the hemagglutinin inhibition (HI) assay by altering receptor specificity and/or antibody-antigen binding. HA molecules containing such substitutions will be useful in the development of diagnostic reference viruses and improved influenza vaccines.

Abstract: The invention provides a composition comprising: an antigen; liposomes; a polyI:C polynucleotide; and a carrier comprising a continuous phase of a hydrophobic substance. Methods for making and using the compositions are also provided.

Abstract: The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to antigens and vaccines useful in prevention of infection by influenza virus. Provided are recombinant protein antigens, compositions, and methods for the production and use of such antigens and subunit vaccine compositions. In some embodiments, influenza antigens include hemagglutinin polypeptides neuraminidase polypeptides, and/or combinations thereof.

Abstract: The invention relates to the production of virosome-like-particles. The invention provides a method for producing a virosome-like-particle comprising contacting an enveloped virus with a solution containing a short-chain phospholipid allowing solubilisation of the viral envelope of said virus further comprising removing short-chain phospholipid from said solution allowing formation of a functionally reconstituted viral envelope.

Abstract: The present invention relates to virosomes comprising hemagglutinin (HA) with improved fusion activity. Preferably, the HA comprised in said virosomes was derived from influenza virus produced in a cell line. The present invention also relates to compositions and a kit comprising the virosomes according to the invention. Further, the present invention relates to uses and methods involving said virosomes, as well as to a method for preparing same.

Abstract: The invention provides human scFv antibodies and monoclonal antibodies that neutralize influenza virus. Also provided are methods of treating and/or preventing a influenza related disease or disorder such bird flu The invention also provides methods of vaccinating a patient against influenza. Also provided are methods of diagnosing influenza-related diseases or disorders and methods of detecting the presence of a influenza in a sample.

Abstract: The present disclosure provides compositions comprising a protein cage and methods for using the protein cage compositions to induce an immune protection response, or to prevent or ameliorate a viral or a bacterial infection.

Abstract: A number of improvements for preparing vaccine antigens from disintegrated influenza viruses are disclosed. A splitting step can be followed by detergent exchange. Splitting can take place in the presence of a buffer with a higher ionic strength and/or in the presence of phosphate buffer.

Abstract: The invention relates to polypeptide carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines are particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: A method for synthesizing influenza virus-like particles (VLPs) within a plant or a portion of a plant is provided. The method involves expression of influenza HA in plants and the purification by size exclusion chromatography. The invention is also directed towards a VLP comprising influenza HA protein and plants lipids. The invention is also directed to a nucleic acid encoding influenza HA as well as vectors. The VLPs may be used to formulate influenza vaccines, or may be used to enrich existing vaccines.

Abstract: The present invention provides an isolated canine influenza virus of subtype H3N8 comprising an HA having SEQ ID NO: 4 or an amino acid sequence that is greater than 99% identical to SEQ ID NO: 4, with the proviso that the amino acids at positions 94 and 233 are identical to SEQ ID NO: 4; a composition comprising attenuated or inactivated virus; isolated or purified HA, NM, NP, M1, NS1, PA, PB1, and PB2 proteins and fragments thereof and compositions comprising same or nucleic acids, optionally as part of a vector, encoding same; and a method of inducing an immune response to canine influenza virus in an animal comprising administering to the animal an aforementioned composition.

Abstract: The invention refers an improved vaccine against infections with pathogens, especially viral pathogens, comprising an antigen, a peptide of the formula R1—XZSZN—XZX—R2 and an immunostimulatory deoxynucleic acid containing deoxyinosine and/or deoxyuridine residues.

Abstract: Provided herein are influenza hemagglutinin stem domain polypeptides, compositions comprising the same, vaccines comprising the same and methods of their use.

Abstract: The instant invention provides methods for determining, predicting and characterizing the genetic variability, emergence and expansion of viruses, in particular, influenza. Accordingly, the invention provides methods for identifying virulent pathogens, genetic mutations within pathogens that are relevant to animal health, and methods and compositions for prophylactic or therapeutic intervention against such pathogens.

Abstract: This invention provides methods of treating and vaccinating against an antigen-expressing tumor and inducing an immune response against a sub-dominant epitope of antigen, comprising a fusion of an LLO fragment to the antigen or a recombinant Listeria strain expressing the antigen. The present invention also provides recombinant peptides comprising a listeriolysin (LLO) protein fragment fused to a Her-2 protein or fragment thereof, recombinant Listeria strains expressing a Her-2 protein, vaccines and immunogenic compositions comprising same, and methods of inducing an anti-Her-2 immune response and treating and vaccinating against a Her-2-expressing tumor, comprising same.

Abstract: Immunogenic compositions comprising partially glycosylated viral glycoproteins for use as vaccines against viruses are provided. Vaccines formulated using mono-, di-, or tri-glycosylated viral surface glycoproteins and polypeptides provide potent and broad protection against viruses, even across strains. Pharmaceutical compositions comprising monoglycosylated hemagglutinin polypeptides and vaccines generated therefrom and methods of their use for prophylaxis or treatment of viral infections are disclosed. Methods and compositions are disclosed for influenza virus HA, NA and M2, RSV proteins F, G and SH, Dengue virus glycoproteins M or E, hepatitis C virus glycoprotein E1 or E2 and HIV glycoproteins gp120 and gp41.

Abstract: A method for synthesizing influenza virus-like particles (VLPs) within a plant or a portion of a plant is provided. The method involves expression of influenza HA in plants and the purification by size exclusion chromatography. The invention is also directed towards a VLP comprising influenza HA protein and plants lipids. The invention is also directed to a nucleic acid encoding influenza HA as well as vectors. The VLPs may be used to formulate influenza vaccines, or may be used to enrich existing vaccines.

Abstract: The present invention includes compositions, methods and kits for inducing an immune response to a tumor and for treating cancer with a Listeria vaccine strain expressing an antigen fused to a truncated LLO protein.

Abstract: An inactivated influenza virus preparation is described which comprises a haemagglutinin antigen stabilised in the absence of thiomersal, or at low levels of thiomersal, wherein the haemagglutinin is detectable by a SRD assay. The influenza virus preparation may comprise a micelle modifying excipient, for example ?-tocopherol or a derivative thereof in a sufficient amount to stabilise the haemagglutinin.

Abstract: The present invention encompasses influenza vaccines, in particular avian influenza vaccines. The vaccine may be a subunit vaccine based on the hemagglutinin of influenza. The hemagglutinin may be expressed in plants including duckweed. The invention also encompasses recombinant vectors encoding and expressing influenza antigens, epitopes or immunogens which can be used to protect animals against influenza. It encompasses also a vaccination regimen compatible with the DIVA strategy, including a prime-boost scheme using vector and subunit vaccines.