Abstract: The present invention describes a combined vaccine that offers broad protection against meningococcal disease caused by the pathogenic bacteria Neisseria meningitidis. The vaccine is comprised of four distinct polysaccharide-protein conjugates that are formulated as a single dose of vaccine. Purified capsular polysaccharides from Neisseria meningitidis serogroups A, C, W-135, and Y are chemically activated and selectively attached to a carrier protein by means of a covalent chemical bond, forming polysaccharide-protein conjugates capable of eliciting long-lasting immunity to a variety of N. meningitidis strains in children as well as adults.

Abstract: The present invention provides a new means of restoring the immune system in aging and immunocompromised individuals using an antioxidant nutraceutical. The nutraceutical stimulates the aging immune system through the Nrf2 master gene regulatory pathway. The invention is based in part on the discovery that the Nrf2 has antioxidant and immune restorative activity. The nutraceutical improves function of both the innate and adaptive immune systems.

Abstract: The disclosure relates to antigenic polypeptides that induce the production of opsonins, in particular opsonic antibodies, and the use of said antigenic polypeptides in vaccines that are protective against human bacterial pathogens.

Abstract: Vaccine compositions in which gangliosides and the OMP of N. meningitidis were combined to form very small size proteoliposomes (VSSP) to be administered subcutaneously are described, these compositions do not require the use of any additional adjuvant. The described compositions allow the immunological treatments with gangliosides, particularly N-AcGM3/VSSP and N-GcGM3/VSSP, showing advantages due to the less aggressive reaction in the site of injection and can be used in a simpler way and better for the patients.

Abstract: The invention provides BASB082, BASB083, BASB091, BASB092 and BASB101 polypeptides and polynucleotides encoding BASB082, BASB083, BASB091, BASB092 and BASB101 polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are diagnostic, prophylactic and therapeutic uses.

Abstract: The subject of the invention is a method for adjuvanting LPS of a Gram-negative bacterium, according to which LPS or LPS liposomes (LPS formulated in liposomes) is (are) mixed with the lipidated human-transferrin receptor subunit B (TbpB protein) of Neisseria meningitidis or a lipidated fragment thereof or (ii) LPS and the lipidated TbpB of N. meningitidis or a lipidated fragment thereof are formulated together in liposomes; or (iii) LPS is conjugated with the lipidated TbpB of N. meningitidis or a lipidated fragment thereof in order to obtain a preparation which does not contain OMVs and which is capable of inducing, after administration to a mammal, an anti-LPS immune response which is improved by comparison with the anti-LPS immune response observed after administration of the corresponding preparation in which the lipidated TbpB of N. meningitidis or a lipidated fragment thereof is omitted; as well as vaccine compositions thereof.

Abstract: The present invention relates to Neisseria ORF2086 proteins, crossreactive immunogenic proteins which can be isolated from nesserial strains or prepared recombinantly, including immunogenic portions thereof, biological equivalents thereof, antibodies that immunospecifically bind to the foregoing and nucleic acid sequences encoding each of the foregoing, as well as the use of same in immunogenic compositions that are effective against infection by Neisseria meningitidis serogroup B.

Abstract: The present invention relates to Neisseria ORF2086 proteins, crossreactive immunogenic proteins which can be isolated from nesserial strains or prepared recombinantly, including immunogenic portions thereof, biological equivalents thereof, antibodies that immunospecifically bind to the foregoing and nucleic acid sequences encoding each of the foregoing, as well as the use of same in immunogenic compositions that are effective against infection by Neisseria meningitidis serogroup B.

Abstract: The present invention relates to Neisseria ORF2086 proteins, crossreactive immunogenic proteins which can be isolated from nesserial strains or prepared recombinantly, including immunogenic portions thereof, biological equivalents thereof, antibodies that immunospecifically bind to the foregoing and nucleic acid sequences encoding each of the foregoing, as well as the use of same in immunogenic compositions that are effective against infection by Neisseria meningitidis serogroup B.

Abstract: The present invention relates to a pharmaceutical vaccine composition comprising: (a) a pathogen-derived antigen selected from the group consisting of Mycobacterium tuberculosis antigen, Bacillus anthracis antigen, HAV (hepatitis A virus) antigen, HBV (hepatitis B virus) antigen, HCV (hepatitis C virus) antigen, HIV (human immunodeficiency virus) antigen, influenza virus antigen, HSV (herpes simplex virus) antigen, Hib (Haemophilus influenzae type b) antigen, Neisseria meningitidis antigen, Corynebacterium diphtheriae antigen, Bordetella pertussis antigen, Clostridium tetani antigen and Varicella virus antigen; (b) a deacylated non-toxic LOS (lipooligosaccharide); and (c) a pharmaceutically acceptable carrier.

Abstract: The present invention relates to a process for stabilizing an adjuvant containing vaccine composition, an adjuvanted vaccine composition in dry form and in particular a process for stabilizing an influenza vaccine composition, particularly an adjuvanted influenza vaccine composition in dry form.

Abstract: The invention relates to a vaccine for the treatment of disease caused by Neisseria, the vaccine including one or more immunogenic components for Neisseria serogroups, as well as antibodies to the immunogenic components and methods of preventing and treating Neisseria infections. The immunogens are based on elements of the inner core lipopolysaccharide.

Abstract: An immunogenic composition comprising the Nm-MIP protein or an immunogenic part thereof or an analogue thereof, wherein the composition is capable of eliciting an immune response when administered to a human or non-human animal, and uses thereof. A pharmaceutical composition or a vaccine composition comprising the Nm-MIP protein or an immunogenic part thereof or an analogue thereof.

Abstract: The invention provides proteins from Neisseria meningitidis, including the amino acid sequences and the corresponding nucleotide sequences. The proteins are predicted to be useful antigens for vaccines and/or diagnostics.

Abstract: The subject of the invention is a method for adjuvanting LPS of a Gram-negative bacterium, according to which LPS or LPS liposomes (LPS formulated in liposomes) is (are) mixed with the lipidated human-transferrin receptor subunit B (TbpB protein) of Neisseria meningitidis or a lipidated fragment thereof; or (ii) LPS and the lipidated TbpB of N. meningitidis or a lipidated fragment thereof are formulated together in liposomes; or (iii) LPS is conjugated with the lipidated TbpB of N. meningitidis or a lipidated fragment thereof; in order to obtain a preparation which does not contain OMVs and which is capable of inducing, after administration to a mammal, an anti-LPS immune response which is improved by comparison with the anti-LPS immune response observed after administration of the corresponding preparation in which the lipidated TbpB of N. meningitidis or a lipidated fragment thereof is omitted; as well as vaccine compositions thereof.

Abstract: The present invention provides a Withania somnifera fraction rich in withanolides and a vaccine comprising a “Withania somnifera fraction” as an adjuvant.

Abstract: Various specific meningococcal proteins are disclosed. The invention provides related polypeptides, nucleic acids, antibodies and methods. These can all be used in medicine for treating or preventing disease and/or infection caused by meningococcus, such as bacterial meningitis.

Abstract: The present invention relates to stable formulations of Neisseria meningitis rLP2086 Subfamily B Antigens in immunogenic compositions. The present invention also relates to methods of preserving the conformation of Neisseria meningitis rLP2086 Antigens and methods for determining the potency of Neisseria meningitis rLP2086 antigens.

Abstract: Polypeptides that can elicit antibodies that are bactericidal for different fHbp variant strains of N. meningitidis, and methods of use, are provided.

Abstract: The present invention generally relates to homogeneous suspensions of small molecule immune potentiators (SMIPs) that are capable of stimulating or modulating an immune response in a subject in need thereof. The homogeneous suspensions may be used in combinations with various antigens or adjuvants for vaccine therapies.

Abstract: The present invention relates to compositions comprising at least one purified PorA protein antigen and at least one purified FetA protein antigen. In particular, said PorA/FetA antigens are antigenically variable antigens comprising the variable regions of PorA/FetA. Specific combinations of PorA/FetA epitopes are presented for example in Table 3. The invention also relates to methods of immunisation comprising administering said compositions, and to methods for producing compositions. Preferably the compositions are purified protein compositions. Preferably the compositions are vaccine compositions.

Abstract: An immunogenic composition comprises (i) an immuno stimulatory oligonucleotide and a polycationic polymer, wherein the oligonucleotide and the polymer ideally associate with each other to form a complex, and (ii) a meningococcal serogroup B antigen. In most embodiments, the composition does not include an aluminium salt and does not include an oil-in-water emulsion.

Abstract: Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus (‘MenB’). This antigen can be efficiently adsorbed to an aluminum hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminum hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminum hydroxyphosphate adjuvant.

Abstract: NMB1870 is a protein in Neisseria meningitidis. Three families of NMB1870 are known. To increase the ability of a NMB1870 protein to elicit antibodies that are cross-reactive between the families, NMB1870 is engineered. Sequences can be substituted from one NMB1870 family into the corresponding position in another family. Proteins of NMB1870 sequences from different families can be joined to each other.

Abstract: This invention provides, among other things, proteins, polypeptides, and fragments thereof, derived from the bacteria Neisseria meningitidis B. Also provided are nucleic acids encoding for such proteins, polypeptides, and/or fragments, as well as nucleic acids complementary thereto e.g., antisense nucleic acids). Additionally, this invention provides antibodies which bind to the proteins, polypeptides, and/or fragments. This invention further provides expression vectors useful for making the proteins, polypeptides, and/or fragments, as well as host cells transformed with such vectors. This invention also provides compositions of the proteins, polypeptides, fragments, and/or nucleic acids, for use as vaccines, diagnostic reagents, immunogenic compositions, and the like. Methods of making the compositions and methods of treatment with the compositions are also provided. This invention also provides methods of detecting the proteins, polypeptides, fragments, and/or nucleic acids.

Abstract: Novel proteins that constitute modified forms of a Neisseria meningitidis surface antigen and encoding nucleic acids are provided. The modified surface proteins are characterized by having deletions of non-conserved amino acids, and thereby being capable of eliciting cross-protective immune responses against Neisseria meningitidis. The invention extends to the use of the modified surface antigens in diagnostics, in therapeutic and prophylactic vaccines and in the design and/or screening of medicaments. The modified surface antigens are particularly useful in vaccines which effectively immunize against a broader spectrum of N. meningitidis strains than would be expected from a corresponding wild-type surface antigen.

Abstract: Compositions for the treatment or prevention of Neisserial infection and methods for their use and manufacture are provided herein.

Abstract: Novel proteins that constitute modified forms of a Neisseria meningitidis surface antigen and encoding nucleic acids are provided. The modified surface proteins are characterized by having deletions of non-conserved amino acids, and thereby being capable of eliciting cross-protective immune responses against Neisseria meningitidis. The invention extends to the use of the modified surface antigens in diagnostics, in therapeutic and prophylactic vaccines and in the design and/or screening of medicaments. The modified surface antigens are particularly useful in vaccines which effectively immunize against a broader spectrum of N. meningitidis strains than would be expected from a corresponding wild-type surface antigen.

Abstract: The meningococcal fhbp gene (encoding factor H binding protein) is naturally expressed from two independent transcripts by two differentially regulated promoters. In one transcript it is co-expressed with the neighbouring upstream gene from the Pnmb1869 promoter. The other transcript is monocistronic and is expressed from its own dedicated promoter, Pfhbp, which is activated by the global regulatory protein FNR in response to oxygen-limiting conditions. To increase expression of the monocistronic transcript a constitutively-active FNR mutant is used. The Pfhbp promoter can thus be activated, leading to over-expression of FNR-activated genes, such as fhbp.

Abstract: A composition comprising (a) Neisseria meningitidis serogroup B outer membrane vesicles (OMVs), and (b) an immunogenic component selected from other Neisseria proteins, or immunogenic fragments thereof. Component (b) preferably includes a protein from a different NmB strain from that from which the OMV of component (a) is derived. The OMVs are preferably obtained by deoxycholate extraction. Optionally, the composition may also comprise a protective antigen against other pathogens.

Abstract: The invention discloses pharmaceutical compositions in liquid form comprising a peptide with the amino acid sequence KLKL5KLK and an oligodeoxynucleotide with the nucleic acid sequence (dIdC)13 and wherein the peptide and the oligodeoxynucleotide are present as sterile-filterable nanoparticles in the composition, thereby forming a suspension, characterized in that the mean particle size of the solid particles is less than 1 ?m.

Abstract: The present invention relates to compositions comprising at least one purified PorA protein antigen and at least one purified FetA protein antigen. In particular, said PorA/FetA antigens are antigenically variable antigens comprising the variable regions of PorA/FetA. Specific combinations of PorA/FetA epitopes are presented for example in Table 3. The invention also relates to methods of immunization comprising administering said compositions, and to methods for producing compositions. Preferably the compositions are purified protein compositions. Preferably the compositions are vaccine compositions.

Abstract: The invention concerns nucleic acids coding for polypeptides specific of the Neisseria genus pathogenic strains, the corresponding polypeptides, and their diagnostic and therapeutic applications.

Abstract: Methods for making and using therapeutic formulations of Proteosome-based immunoactive compositions are provided. The immunogenic compositions, which include Proteosomes and liposaccharides, may be used to elicit or enhance a nonspecific innate immune response to, for example, treat or prevent infectious disease. In addition, after activating the innate immune system, immunogenic compositions further containing an antigen may be used to elicit a specific adaptive immune response. Furthermore, provided are compositions capable of altering hyperreactive responses or inflammatory immune responses, such as allergic reactions. Such compositions may be used as a prophylactic, or in various clinical settings to treat or prevent infectious disease (such as parasite, fungal, bacterial or viral infections), or to alter inappropriate inflammatory immune responses (such as allergic reactions or asthma).

Abstract: The invention provides proteins from Neisseria meningitidis (strains A & B) and from Neisseria gonorrhoeae, including amino acid sequences, the corresponding nucleotide sequences, expression data, and serological data. The proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics.

Abstract: The invention provides methods of formulating an anti-inflammatory composition for treating inflammatory conditions in a specific organ or tissue. The method involves selecting at least one pathogen that is pathogenic in the specific organ or tissue; producing an antigenic composition comprising antigenic determinants that together are specific for the pathogen; and formulating the antigenic composition for administration as an anti-inflammatory composition capable of eliciting an anti-inflammatory response in the specific organ or tissue. In embodiments of the invention the pathogen may be an endogenous pathogen, such as an endogenous bacterial pathogen. The pathogen may be an exogenous pathogen, such as a bacterial pathogen, viral pathogen, a fungal pathogen, or a helminth pathogen.

Abstract: The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

Abstract: A composition comprising (a) Neisseria meningitidis serogroup B outer membrane vesicles (OMVs), and (b) an immunogenic component selected from other Neisseria proteins, or immunogenic fragments thereof. Component (b) preferably includes a protein from a different NmB strain from that from which the OMV of component (a) is derived. The OMVs are preferably obtained by deoxycholate extraction. Optionally, the composition may also comprise a protective antigen against other pathogens.

Abstract: NMB1870 is a protein in Neisseria meningitidis. Three families of NMB1870 are known. To increase the ability of a NMB1870 protein to elicit antibodies that are cross-reactive between the families, NMB1870 is engineered. Sequences can be substituted from one NMB1870 family into the corresponding position in another family. Proteins of NMB1870 sequences from different families can be joined to each other.

Abstract: The present invention relates to the field of neisserial vaccine compositions, their manufacture, and the use of such compositions in medicine. More particularly it relates to processes of making novel engineered meningococcal strains which are more suitable for the production of neisserial, in particular meningococcal, outer-membrane vesicle (or bleb) vaccines. Advantageous processes and vaccine products are also described based on the use of novel LOS subunit or meningococcal outer-membrane vesicle (or bleb) vaccines which have been rendered safer and/or more effective for use in human subjects. In particular combinations of gene downregulations are described such as PorA and OpA, PorA and OpC, OpA and OpC, and PorA and OpA and OpC. Alternatively, or in addition, lgtB? is shown to be an optimal mutation for effectively and safely using L3 and/or L2 LOS in Neisseria vaccine compositions.

Abstract: Immunogenic compositions (e.g. vaccines) comprising: (a) an immunostimulating amount of a Neisseria antigen (preferably N. meningitidis serogroup B); and (b) an immunostimulating amount of an adjuvant composition comprising an oligonucleotide comprising at least one CG motif. Component (b) may further comprise a second adjuvant. Component (a) may be selected from a variety of antigens. Adjuvant compositions comprising an oligonucleotide having at least one CG motif, and complete Freund's adjuvant (CFA) are also provided.

Abstract: The invention provides BASB082, BASB083, BASB091, BASB092 and BASB101 polypeptides and polynucleotides encoding BASB082, BASB083, BASB091, BASB092 and BASB101 polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are diagnostic, prophylactic and therapeutic uses.

Abstract: Mucosal immunization using one or more antigens following parenteral administration of the same or different antigens is described.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a cancer cell. Delivery of the cargo compound is accomplished by the use of protein transduction domains derived from cupredoxins. The invention further discloses methods for treating cancer and diagnosing cancer.

Abstract: The invention relates to a vaccine against N. meningitidis infections, comprising (i) an N. meningitidis LOS especially consisting of a lipid A, an inner core, and an L8-type ? chain in which the heptose II residue of the inner core (a) carries a phosphoethanolamine (PEA) substituent in position O-3, and does not carry a PEA substituent in positions O-6 and O-7, or (b) carries a phosphoethanolamine (PEA) substituent in position O-3 and in position O-6 or O-7; and (ii) the lipidated sub-unit B (TbpB) of the receptor of the human transferrine of an N. meningitidis strain or a lipid fragment of said TbpB.

Abstract: Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus (‘MenB’). This antigen can be efficiently adsorbed to an aluminium hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminium hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant.

Abstract: The invention relates to a vaccine for the treatment of disease caused by Neisseria, the vaccine including one or more immunogenic components for Neisseria serogroups, as well as antibodies to the immunogenic components and methods of preventing and treating Neisseria infections. The immunogens are based on elements of the inner core lipopolysaccharide.

Abstract: Immunogenic compositions containing phospholipid adjuvants, including microparticle and emulsion compositions. According to one aspect of the invention, an immunogenic microparticle composition is provided comprising: water; a polymer microparticle; an antigen adsorbed to the microparticle; and a phospholipid compound, e.g., a synthetic phospholipid compound comprising: (i) one or more phosphoryl groups independently selected from a phosphato group and a phosphodiester group; (ii) a plurality of linear alkane groups. According to another aspect of the invention an immunogenic emulsion composition is provided that comprises: water; a metabolizable oil; an emulsifying agent; an antigen; and a phospholipid compound, e.g., a synthetic phospholipid compound like that above. The emulsion composition is an oil-in-water emulsion having oil and aqueous phases, in which the oil phase is in the form of oil droplets, substantially all of which are less than 1 micron in diameter.

Abstract: Methods for making and using therapeutic formulations of Proteosome-based immunoactive compositions are provided. The immunogenic compositions, which include Proteosomes and liposaccharides, may be used to elicit or enhance a nonspecific innate immune response to, for example, treat or prevent infectious disease. In addition, after activating the innate immune system, immunogenic compositions further containing an antigen may be used to elicit a specific adaptive immune response. Furthermore, provided are compositions capable of altering hyperreactive responses or inflammatory immune responses, such as allergic reactions. Such compositions may be used as a prophylactic, or in various clinical settings to treat or prevent infectious disease (such as parasite, fungal, bacterial or viral infections), or to alter inappropriate inflammatory immune responses (such as allergic reactions or asthma).

Abstract: The invention relates to a vaccine for the treatment of disease caused by Neisseria, the vaccine including one or more immunogenic components for Neisseria serogroups, as well as antibodies to the immunogenic components and methods of preventing and treating Neisseria infections. The immunogens are based on elements of the inner core lipopolysaccharide.