Abstract: The present invention relates to the branch of Biotechnology and Medicine, particularly to a method for the selection and treatment of patients with carcinomas of epithelial origin that co-express the HER1 and HER2 receptors without increased expression of these receptors or with the presence of RAS activating mutations. In particular, this method is based on the application of bivalent vaccine compositions which have as active principle the extracellular domains of the HER1 and HER2 receptors or portions thereof and as an adjuvant the very small proteoliposomes derived from the outer membrane proteins of Neisseria meningitidis and the GM3 ganglioside. This method is useful for the treatment of patients whose expression levels of HER1 and HER2 do not allow the monoclonal antibodies against HER1 and/or HER2 to have a therapeutic effect.

Abstract: The present invention relates to an immunomodulator for the prevention or treatment of an allergic disease caused by house dust mite-derived allergens. Particularly, the present invention provides an immunomodulatory pharmaceutical composition comprising as an effective ingredient a bacteria extracellular vesicle containing an allergens derived from North American house dust mite or European house dust mite, and a preparation method therefor.

Abstract: The present invention relates to in vitro methods for producing Neisseria meningitidis capsular polysaccharides which have a defined length. The present invention also relates to compositions comprising at least one capsule polymerase, at least one donor carbohydrate and at least one acceptor carbohydrate, wherein the ratio of donor carbohydrate to acceptor carbohydrate is a ratio from 10:1 to 400:1. Moreover, the present invention provides truncated versions of the capsule polymerases of Neisseria meningitidis serogroups A and X. Also provided herein are pharmaceuticals, in particular vaccines, comprising the synthetic capsular polysaccharides of Neisseria meningitidis which have a defined length. Furthermore, the invention provides for methods for the production of said vaccines.

Abstract: A first aspect of the invention provides meningococcal outer membrane vesicles in which NHBA is over-expressed. A second aspect of the invention provides meningococcal outer membrane vesicles in which NadA is over-expressed. A third aspect of the invention provides a panel of bacterial strains, each member of which is isogenic except for a single gene which in each strain encodes a different variant antigen of interest.

Abstract: The present disclosure generally relates to methods of preparing nicotine and resolving R,S nicotine to enrich the (S)(?) enantiomer. The method may comprise combining N-methyl-2-pyrrolidone or a salt thereof with a nicotinate compound in the presence of a solvent and a strong base to form 1-methyl-3-nicotinoyl-2-pyrrolidone or a salt thereof; and reducing the 1-methyl-3-nicotinoyl-2-pyrrolidone or salt thereof in solution with Na2S2O4 to produce racemic nicotine or salt thereof. Resolving the racemic nicotine (or other enantiomeric mixture) may comprise combining the nicotine with (?)-O,O?-di-p-toluoyl-L-tartaric acid (L-PTTA).

Abstract: Two Vi conjugates have been prepared by carbodiimide-mediated synthesis, using adipic acid dihydrazide derivatized CRM197 (a non-toxic variant of diphtheria toxin) and tetanus toxoid, as carrier proteins.

Abstract: Factor H binding proteins that can elicit antibodies that are bactericidal for at least one strain of N. meningitidis, and methods of use of such proteins, are provided.

Abstract: Compositions comprising a first biological molecule from a Neisseria bacterium and a second biological molecule from a Neisseria bacterium. The term “biological molecule” includes proteins and nucleic acids. Preferred Neisseria species are N. meningitidis and N. gonorrhoeae.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a brain cancer cell and/or across the blood-brain barrier. Delivery of the cargo compound is accomplished by the use of protein transport peptides derived from Neisseria outer membrane proteins, such as Laz. The invention also provides synthetic transit peptides comprised of the pentapeptide AAEAP. The invention further discloses methods for treating cancer, and specifically brain cancer, as well as other brain-related conditions. Further, the invention provides methods of imaging and diagnosing cancer, particular brain cancer.

Abstract: The present application relates to a composition including gut flora-derived extracellular vesicles, and to an animal disease model using same. In addition, the present application relates to a method for using the gut flora-derived extracellular vesicles to efficiently search for a candidate drug which may prevent or treat diseases that occur due to gut flora-derived extracellular vesicles, and to a vaccine which can efficiently prevent or treat infections caused by gut flora or diseases that occur due to gut flora-derived extracellular vesicles. Further, the development of diagnostic technology to discover, using the gut flora-derived extracellular vesicles of the present application, the etiology of diseases that occur due to gut flora-derived extracellular vesicles, can be achieved.

Abstract: The present invention relates to the use of mutant glycoproteins from pathogenic bacteria lacking one or more phosphorylcholine and/or glycosylation post-translational modifications as immunogens. These post-translational modifications act as masking structures that elicit an immune response which does not confer protection on an infected individual. The removal or modification of these masking structures alters the protein such that it elicits a stronger immune response to the protein and/or the bacterial pathogen. Particular examples are pilin proteins and nitrite reductase glycoproteins of Neisseria bacteria.

Abstract: Two or more Neisserial proteins are joined such that they are translated as a single polypeptide chain. Hybrid proteins are represented by the formula NH2-A-[-X-L-]n-B—COOH where X is an amino acid sequence, L is an optional linker amino acid sequence. A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, and n is an integer greater than 1. Proteins where each of the n —X— moieties shares sequence identity to each other —X— moiety, the protein is a ‘tandem protein’.

Abstract: The present invention generally provides methods and vaccines for the prevention of diseases caused by Neisseria meningitidis bacteria, particularly serogroup B strains.

Abstract: The invention provides immunogenic compositions comprising (a) a capsular saccharide antigen from serogroup C of N. meningitidis, and (b) a chitosan adjuvant. The composition preferably comprises (c) one or more further antigens and/or (d) one or more further adjuvants. The compositions are particularly suitable for mucosal delivery, including intranasal delivery. The invention also provides immunogenic compositions for mucosal delivery comprising capsular saccharides from at least two of serogroups A, C, W135 and Y of N. meningitidis. It is preferred that the capsular saccharides in the compositions of the invention are conjugated to carrier protein(s) and/or are oligosaccharides. Conjugated oligosaccharide antigens are particularly preferred.

Abstract: The present invention encompasses methods, assays and kits for the detection of pathogenic bacteria in a patient and for the differential diagnosis of pulmonary diseases associated with pathogenic bacteria from pulmonary diseases not associated with pathogenic bacteria.

Abstract: An immunological adjuvant comprises an aluminum salt, an immunostimulatory oligonucleotide and a polycationic polymer, wherein the oligonucleotide and the polymer ideally associate with each other to form a complex. The adjuvant can be included in a composition with an immunogen e.g. to elicit an immune response that protects against a bacterial disease or a fungal disease.

Abstract: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilized using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilization of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from both serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.

Abstract: The present invention relates to an immuno-protective and non-toxic Gram-negative bleb vaccine suitable for paediatric use. Examples of the Gram-negative strains from which the blebs are made are N. meningitidis, M. catarrhalis and H. influenzae. The blebs of the invention are improved by one or more genetic changes to the chromosome of the bacterium, including up-regulation of protective antigens, down-regulation of immunodominant non-protective antigens, and detoxification of the Lipid A moiety of LPS.

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: OMVs targeted against specific epidemic strains can be highly effective in controlling localized outbreaks of disease. In combination with large-scale and reproducible manufacturing techniques, a vaccine can be rapidly produced after an outbreak. The invention provides a method for preparing a meningococcal outer membrane vesicle (OMV) vaccine, comprising the steps of: (i) identifying the serosubtype of a meningococcal strain associated with an outbreak of meningococcal meningitis; (ii) preparing OMVs from a meningococcal strain having the serosubtype identified in step (i) for use in vaccine manufacture. The method may comprise one or both of the further steps of (iii) formulating said OMVs as a vaccine; and (iv) distributing said vaccine in a geographical area affected by or likely to be affected by said outbreak. The meningococcal strain will typically be in serogroup B, but may be instead by in serogroup A, C, W135, Y, etc.

Abstract: Various improvements to vaccines that include a serogroup C meningococcal conjugate antigen, including: (a) co-administration with acellular B. pertussis antigen; (b) co-administration with an inactivated poliovirus antigen; (c) supply in a kit together with a separate pneumococcal conjugate component, which may be in a liquid form; and (d) use in combination with a pneumococcal conjugate antigen but without an aluminum phosphate adjuvant. A kit may have: (a) a first immunogenic component that comprises an aqueous formulation of a conjugated capsular saccharide from Streptococcus pneumoniae; and (b) a second immunogenic component that comprises a conjugated capsular saccharide from Neisseria meningitidis serogroup C.

Abstract: Uses of BMP-1 isoforms for diagnosing and treating defects and disorders of bone and soft tissues are described. Also described is a newly isolated variant of the BMP-1 isoform BMP-1-3.

Abstract: The present invention relates to a method of coating a spore with one or more therapeutic agents. The present invention also relates to a coated spore obtained by the method of the present invention and the use of the coated spore as a vaccine.

Abstract: A small number of defined antigens can provide broad protection against meningococcal infection, and the invention provides a composition which, after administration to a subject, is able to induce an antibody response in that subject, wherein the antibody response is bactericidal against two or three of hypervirulent lineages A4, ET 5 and lineage 3 of N. meningitidis serogroup B. Rather than consisting of a single antigen, the composition comprises a mixture of 10 or fewer purified antigens, and should not include complex or undefined mixtures of antigens such as outer membrane vesicles. Five protein antigens are used in particular: (1) a ‘NadA’ protein; (2) a ‘741’ protein; (3) a ‘936’ protein; (4) a ‘953’ protein; and (5) a ‘287’ protein.

Abstract: The present invention relates to immunogenic compositions for modulating the immune system, comprising a therapeutically effective quantity of two or more immuno-active antigenic agents with pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs) and one or more physiologically acceptable carriers, excipients, diluents or solvents. The immunogenic compositions according to the present invention are used for producing medicaments for preventing and/or treating, and for preventing and/or treating infectious diseases, auto-immune diseases, allergic diseases, inflammation, arthritis, inflammatory diseases, transplant rejection, affections caused by vascular disorders, diseases caused by haemorrhagic or ischaemic cardiovascular accidents, ischaemia, heart attack and haemorrhagia leading to tissue destruction, heart, kidney, respiratory or liver insufficiency, cancer, malign and benign tumours and neoplasia.

Abstract: The invention provides proteins from gonococcus (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. They are also useful for distinguishing between gonococcus and meningococcus and, in particular, between gonococcus and serogroup B meningococcus.

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 discloses methods and materials for delivering a cargo compound into a brain cancer cell and/or across the blood-brain barrier. Delivery of the cargo compound is accomplished by the use of protein transport peptides derived from Neisseria outer membrane proteins, such as Laz. The invention also provides synthetic transit peptides comprised of the pentapeptide AAEAP. The invention further discloses methods for treating cancer, and specifically brain cancer, as well as other brain-related conditions. Further, the invention provides methods of imaging and diagnosing cancer, particular brain cancer.

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: The present invention relates to immunogenic compositions and vaccines for the treatment and prevention of Neisserial disease. Immunogenic compositions of the invention comprise the Hsf (also called Msf) and Opc neisserial antigens. These antigens have been found to be the two mechanisms by which Neisseria meningitidis binds host vitronectin (in order to promote adhesion and/or to evade host complement mediated killing). Vaccines comprising both antigens can thus advantageously result in an immune response which is better able to kill neisserial strains and otherwise prevent vitronectin-related neisserial complement mediated killing resistance and/or neisserial adhesion events required for pathogenesis.

Abstract: The present application discloses an immunogenic composition comprising a Hib saccharide conjugate, at least one additional bacterial, for example N. meningitidis, saccharide conjugate(s), and a further antigen selected from the group consisting of whole cell pertussis and hepatitis B surface antigen, wherein the saccharide dose of the Hib saccharide conjugate is less than 5 ug.

Abstract: Immunogenic compositions and methods of their use, as well as processes for their production are provided herein.

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 present invention provides non-toxic Gram-negative bacteria. In particular, the present invention provides viable Gram-negative bacteria (e.g., E. coli) substantially lacking lipopolysaccharide (LPS, endotoxin) within the outer membrane. The present invention further provides methods of generating viable non-toxic Gram-negative bacteria and uses thereof. The present invention also provides compositions and methods for inducing immune responses and for researching and developing therapeutic agents.

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 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: The invention provides a novel class of compounds, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 7. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness of a vaccine.

Abstract: The present invention relates to a method of coating a spore with one or more therapeutic agents. The present invention also relates to a coated spore obtained by the method of the present invention and the use of the coated spore as a vaccine.

Abstract: The present invention is directed to nucleic acids encoding glycosyltransferases, the proteins encoded thereby, and to methods for synthesizing oligosaccharides using the glycosyltransferases of the invention. In particular, the present application is directed to identification a glycosyltransferase locus of Neisseria gonorrhoeae containing five open reading frames for five different glycosyltransferases. The functionally active glycosyltransferases of the invention are characterized by catalyzing reactions such as adding Gal ?1?4 to GlcNAc or Glc; adding GalNAc or GlcNAc ?1?3 to Gal; and adding Gal ?l?4 to Gal. The glycosyltransferases of the invention are particularly suited to the synthesis of the oligosaccharides Gal?1?4GlcNAc?1?3Gal?1?4Glc (a mimic of lacto-N-neotetraose), GalNAc?1?3Gal?1?4GlcNAc?1?3Gal?1?4Glc?1?4 (a mimic ganglioside), and Gal?1?4Gal?1?4Glc?1?4Hep?R (a mimic of the saccharide portion of globo-glycolipids).

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: The present invention discloses methods and materials for delivering a cargo compound into a brain cancer cell and/or across the blood-brain barrier. Delivery of the cargo compound is accomplished by the use of protein transport peptides derived from Neisseria outer membrane proteins, such as Laz. The invention also provides synthetic transit peptides comprised of the pentapeptide AAEAP (SEQ ID NO: 25). The invention further discloses methods for treating cancer, and specifically brain cancer, as well as other brain-related conditions. Further, the invention provides methods of imaging and diagnosing cancer, particularly brain cancer.

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: 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 present invention discloses a Gram negative bacterium in which the expression of a protein involved in LPS transport to the outer membrane is functionally down-regulated such that the level of LPS in the outer membrane is decreased compared to a wild-type Gram negative bacterium. Down regulation of Imp and MsbA proteins can result in such a bacterium. Outer membrane vesicle preparations derived from the Gram negative bacterium of the invention can be used in vaccines to provide protection against bacterial infection.

Abstract: GPC (gel permeation chromatography) and size exclusion chromatography with detection by multi-angle light scattering photometry (SEC-MALS) can be used to accurately measure molecular size and molar mass, respectively, of saccharide conjugates. The invention provides (a) a process for measuring the molecular size of a conjugated saccharide antigen within a sample, comprising a step of analyzing the sample by GPC, and (b) a process for measuring the molar mass of a conjugated saccharide antigen within a sample, comprising a step of analysing the sample by SEC-MALS.

Abstract: The present invention generally provides methods and compositions for eliciting an immune response against Neisseria spp. bacteria in a subject, particularly against a Neisseria meningitidis serogroup B strain.

Abstract: The present invention relates to immunogenic compositions and vaccines for the treatment and prevention of Neisserial disease. Immunogenic compositions of the invention contain combinations of antigens selected from at least two different classes of antigens including adhesins, autotransporter proteins, toxins, iron acquisitions proteins and membrane-associated protein (preferably integral outer membrane protein)s. Such combinations of antigens are able to target the immune response against different aspects of the neisserial life cycle, resulting in a more effective immune response.

Abstract: A combination of CpG oligonucleotides and polymer microparticles is an extremely effective adjuvant for Neisserial antigens. The invention therefore provides a composition comprising: (a) a Neisserial antigen; (b) a CpG oligonucleotide; and (c) a biodegradable polymer microparticle.