Abstract: Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response.

Abstract: Provided herein are methods of producing neutralizing monoclonal antibodies, by cyclical immunization, that cross-react with strains of Influenza virus of the same subtype or different subtypes. Also provided herein are compositions comprising such antibodies and methods of using such antibodies to diagnose, prevent or treat Influenza virus disease.

Abstract: The present invention relates to biologically active compositions and methods for the lyophilization and reconstruction of virosomes comprising special membrane compositions. These compositions are essential to the invention and provide superior freeze-drying stress-resistance for the virosomes of the invention.

Abstract: A novel adjuvant composition is provided that is excellent in safety and convenience as compared to the conventional adjuvant such as Alum. An adjuvant composition comprising citrullines, which are water soluble substance present in the living body, and/or a salt thereof; a vaccine composition comprising said adjuvant composition and an antigen; a process for preparing said adjuvant composition and said vaccine composition; and a method for administering said adjuvant composition and said vaccine composition are provided.

Abstract: The present invention relates to novel hemagglutinin H5 proteins, nucleic acids and vectors encoding for those as well as vaccines comprising any of such H5 proteins, nucleic acids or vectors encoding for those H5 proteins. Moreover, the present invention also relates to the medicinal use of any of such compositions in humans and animals.

Abstract: Bacterial flagellin protein is modified to improve adjuvant activity.

Abstract: The present invention relates to methods of improving the stability and maintaining the potency of recombinant hemagglutinin formulations, in particular, recombinant influenza hemagglutinin (rHA). In particular, Applicants have shown that the stability of rHA formulations may be significantly improved by mutating cysteine residues or by formulating with a reducing agent and sodium citrate.

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: The present invention relates to vaccines comprising at least one mRNA encoding at least one antigen for use in the treatment of a disease in an elderly patient preferably exhibiting an age of at least 50 years, more preferably of at least 55 years, 60 years, 65 years, 70 years, or older, wherein the treatment comprises vaccination of the patient and eliciting an immune response in said patient. The present invention is furthermore directed to kits and kits of parts comprising such a vaccine and/or its components and to methods applying such a vaccine or kit.

Abstract: Influenza vaccines are administered using solid biodegradable microneedles. The microneedles are fabricated from the influenza vaccine in combination with solid excipient(s) and, after penetrating the skin, they dissolve in situ and release the vaccine to the immune system. The influenza vaccine is (i) a purified influenza virus surface antigen vaccine, rather than a live vaccine or a whole-virus or split inactivated vaccine (ii) an influenza vaccine prepared from viruses grown in cell culture, not eggs, (iii) a monovalent influenza vaccine e.g. for immunizing against a pandemic strain, (iv) a bivalent vaccine, (v) a tetravalent or >4-valent vaccine, (vi) a mercury-free vaccine, or (vii) a gelatin-free vaccine.

Abstract: Provided herein are methods for generating dry vaccine powder formulations. Dry vaccine powder formulations can be used for intranasal delivery. Also provided are methods for stimulating local mucosal and systemic immunity by intranasal vaccine delivery.

Abstract: The invention relates to the use of a trivalent, non-live influenza antigen preparation, particularly a split influenza preparation, in the manufacture of a one-dose influenza vaccine for intradermal delivery. In particular, the invention relates to the use of split influenza preparations wherein the vaccine comprises at least one non-ionic surfactant selected from the group consisting of the octyl-or nonylphenoxy polyoxyethanols (for example the commercially available Triton™ series), polyoxyethylene sorbitan esters (Tween™ series) and polyoxyethylene ethers or esters of general formula (I): HO(CH2CH2O)n-A-R, wherein n is 1-50, A is a bond or —C(O)—, R is C1-50 alkyl or phenyl C1-50 alkyl; and combinations of two or more of these.

Abstract: An intraorally administrable vaccine composition useful to be a preventive or therapeutic agent for infectious diseases, and effectively induces a systemic immune response or a mucosal immune response is provided. A vaccine composition for administration to the oral cavity of a human or an animal, the vaccine composition containing at least one antigen derived from an infectious disease, and at least one selected from the group consisting of a toll-like receptor 4 (TLR4) agonist, a toll-like receptor 2/6 (TLR2/6) agonist, and cyclic dinucleotide, or a derivative or salt thereof.

Abstract: The invention relates to the generation of a new class of virosome particles, making use of virus antigens expressed in plant, particularly influenza antigens, and to vaccines, particularly influenza vaccines, containing these virosome particles.

Abstract: The invention provides an isolated H3 equine influenza A virus, as well as methods of preparing and using the virus, and genes or proteins thereof.

Abstract: Described are methods for vaccinating a subject against influenza comprising administering a vaccine multiple times to a subject where the vaccine comprises influenza hemagglutinin (HA) and neuraminidase (NA) proteins from at least a first influenza strain, wherein the HA and NA proteins of the first influenza strain are administered to the subject at least three times within a period of less than one year. Such immunization schemes induce cross-protection against heterologous and heterosubtypic influenza strains.

Abstract: The compound N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide is a useful drug compound for enhancing immune response and can be used, for example, as a vaccine adjuvant and a cancer treatment.

Abstract: An antigen concentration procedure does not involve lyophilisation of a bulk antigen before its final formulation and/or delivery. Thus a process for preparing a vaccine comprises steps of (i) increasing the concentration of an antigen in a liquid composition including that antigen, to provide a concentrated antigen, and (ii) formulating a vaccine from the concentrated antigen. The concentrated antigen is not lyophilised between or during steps (i) and (ii). The invention is particularly useful for preparing solid vaccine forms.

Abstract: Embodiments of the present invention generally disclose methods, compositions and uses for generating and expressing poxvirus constructs. In some embodiments, constructs may contain an influenza virus gene segment. In certain embodiments, methods generally relate to making and using compositions of constructs including, but not limited to, poxvirus vaccine compositions having two or more influenza gene segments. In other embodiments, vaccine compositions are reported of use in a subject.

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: 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: 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 plant 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 invention relates to virosome-based influenza vaccines for the manufacture of medicaments that are administered intradermally in humans. The invention provides (trivalent) compositions comprising low doses of hemagglutinin (HA) antigen in a virosomal preparation that fulfill the immune response standards with respect to seroconversion rates, GMT-fold increase and protection rates, for use in vaccination set-ups.

Abstract: Described herein is the development of a computationally optimized influenza HA protein that elicits broadly reactive immune response to all H5N1 influenza virus isolates. The optimized HA protein was developed through a series of HA protein alignments, and subsequent generation of consensus sequences, for clade 2 H5N1 influenza virus isolates. The final consensus HA amino acid sequence was reverse translated and optimized for expression in mammalian cells. It is disclosed herein that influenza virus-like particles containing the optimized HA protein are an effective vaccine against H5N1 influenza virus infection in animals.

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 plant 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: Methods that stimulate a protective immune response in a subject include a portion of a protein from a naturally occurring viral hemagglutinin, wherein the protein portion includes at least a portion of a globular head and at least a portion of at least one secondary structure that causes the globular head to essentially retain its tertiary structure, and wherein the protein portion lacks a transmembrane domain, a cytoplasmic domain and an HA2 subunit. Compositions administered to the subject can further include a carrier and can be administered in single or multiple doses.

Abstract: The present disclosure provides a method of inducing a cross-protective immune response in a subject against a pathogen, such as influenza, comprising administering a first unique pathogen antigen to the subject; and administering a second unique pathogen antigen 3-52 weeks after a); wherein the second unique pathogen antigen and the first unique pathogen antigen are immunologically distinct but share conserved sites that are not normally immunogenic for antibodies. Also disclosed herein are assays for detecting cross-protective antibodies, methods of generating novel cross-protective antibodies. Further provided are novel antibodies against influenza.

Abstract: The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable).

Abstract: The invention provides novel compositions comprising imidazoquinoxaline compounds of formula (I) and analogs thereof. Also provided are methods of administering the compositions in an effective amount to enhance the immune response of a subject. Further provided are novel compositions and methods of administering the compositions in combination with (an) other agent(s).

Abstract: This disclosure relates to compositions and methods for inducing immune response. Specifically, the disclosure relates to a composition comprising a subunit antigen stabilized by a polysaccharide-containing plant extract, in which the antigen consists of virus-like particles that have enhanced mucosal immuno-genicity as a result of the stabilization.

Abstract: Methods of making and compositions that stimulate a protective immune response in a subject include a portion of a protein from a naturally occurring viral hemagglutinin, wherein the protein portion includes at least a portion of a globular head and at least a portion of at least one secondary structure that causes the globular head to essentially retain its tertiary structure, and wherein the protein portion lacks a membrane fusion domain, a transmembrane domain and a cytoplasmic domain. Compositions can further include a Toll-like Receptor agonist and a carrier protein.

Abstract: Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.

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.

Abstract: This invention discloses a method of increasing production of virus-like particles comprising expressing an avian influenza matrix protein. The invention also comprises methods of making and using said VLPs.

Abstract: Disclosed herein are immunogenic compositions for producing immediate and sustained immunity to infectious viral and bacteriological pathogens. A univalent immunogenic composition is disclosed comprising an isolated antigen and a polynucleotide formulated into a nanoparticle or liposome. Furthermore, multivalent immunogenic compositions are disclosed comprising multiple univalent immunogenic compositions. Also disclosed, are methods of inducing protective or therapeutic immune responses in individuals comprising administering one or more univalent immunogenic compositions.

Abstract: Methods of stabilizing solutions with enveloped vims-based virus-like particles containing an influenza antigen and such stabilized solutions are described.

Abstract: The present invention includes influenza Hemagglutinin protein fragments that fold properly when expressed in bacteria.

Abstract: A viral vaccine, specifically an influenza vaccine, comprises a combination of a component (a1) represented by a detoxified or non-toxic mutant of subunit A of an AB type exotoxin, and a component (a2) represented by at least one substance selected from the group consisting of metal salts and mineral salts, in association with a viral immunogen.

Abstract: Described are methods for separating hemagglutinin (HA) antigens, comprising the steps of applying a reduced and derivatized antigen preparation comprising solubilized HA antigens and a detergent in a pH controlled solution, on a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) column; and eluting the HA antigens from the column with an ion pairing agent in an organic mobile phase. The invention further relates to quantifying methods using the methods for separating the antigens with the further step of measuring the peak area of the eluted antigen in a chromatogram resulting from the elution step.

Abstract: A combination of ultrafiltration and HPLC is used to analyze influenza virus. This combination is able to quantify hemagglutinin (HA) and correlates well with single radial immunodiffusion (SRID) results, but can be performed without the delay of waiting for immunochemical SRID reagents.

Abstract: The invention relates to adjuvanted vaccine formulations, in particular influenza vaccines for intranasal delivery. Provided is an adjuvanted influenza vaccine formulation, comprising (i) peptidoglycan microparticles obtained from a Gram-positive bacterium and (ii) at least one influenza virus antigen or antigenic preparation thereof, which antigen or antigenic preparation is not fused or otherwise covalently attached to a proteinaceous peptidoglycan binding moiety.

Abstract: A process for producing a split influenza virus preparation or subunit influenza preparation comprising the steps of: (i) providing a whole virus preparation; (ii) splitting the whole virus preparation in the presence of a first detergent; (iii) adding t-octylphenoxypolyethoxyethanol (TRITON X-100™) to the resulting split virus preparation; and (iv) filtering the split virus preparation.

Abstract: The present invention provides, among other things, methods, reagents, and systems for the treatment, detection, analysis, and/or characterization of influenza infections.

Abstract: The immune response to an antigen of interest, either in purified form or expressed via an alphavirus replicon particle, can be enhanced by the simultaneous administration of an alphavirus replicon particle which expresses interleukin-12. This allows for the use of significantly smaller quantities of the antigen and this immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

Abstract: The present invention provides a system for analyzing interactions between glycans and interaction partners that bind to them. The present invention also provides HA polypeptides that bind to umbrella-topology glycans, and reagents and methods relating thereto.

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

Abstract: Disclosed are antibodies that bind to the stem region of influenza hemagglutinin in the neutral pH conformation, hemagglutinin epitopes in the stem region, and methods of making and using both.

Abstract: A method of quickly producing a vaccine for a biotype of pathogenic microorganism is described, where a nucleic acid molecule or fragment thereof is obtained from a biological sample from an animal exposed to the microorganism, a protective molecule is prepared based on the nucleic acid molecule of interest or fragment thereof, and administered to an animal which has been or is as risk of being exposed to the microorganism. A protective response to the biotype of the microorganism is obtained in the animal.

Abstract: An influenza vaccine includes an increased amount of H3N2 antigen relative to the normal dose. In a typical embodiment, the vaccine includes hemagglutinins from an A/H1N1 strain, an A/H3N2 strain, and a B strain, wherein (i) the weight ratio of H3N2:H1N1 hemagglutinin is greater than 1 and (ii) the weight ratio of H3N2:B hemagglutinin is greater than 1. In such a vaccine the weight ratio of H1N1:B hemagglutinin will normally be 1. For example, a vaccine may contain hemagglutinin at 15 ?g for A/H1N1, 30 ?g for A/H3N2 and 15 ?g for B.