Abstract: The present invention is directed to a bio-functionalized stimulus-responsive dissolvable PEG-hydrogel. This inventive stimulus-responsive dissolvable PEG-hydrogel comprises a matrix of PEG-polymers, which are modified to contain at least one multifunctional fusion protein, the multifunctional fusion protein preferably comprising as components a substrate binding peptide (SBP), preferably a repetitive RGD-binding peptide and/or a ZZ-binding domain, preferably a tag for purification, and at least one N- and/or C-terminal linker. The present invention is furthermore directed to the use of such inventive stimulus-responsive dissolvable PEG-hydrogels in the treatment of lesions, in surgical dressings, for wound treating, for soft and hard tissue regeneration, for the treatment of wounds in the oral cavity, in the field of ophthalmology, in the field of periodontal defects, etc. The invention also describes a method of treatment for such diseases.

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: An immunogenic composition comprising a siderophore covalently linked to a pharmaceutically acceptable carrier molecule wherein the antigenicity of the siderophore moiety is sufficient to stimulate an immunologic response to the siderophore when the composition is circulating in the bloodstream of a human or non-human animal and vaccine.

Abstract: The invention provides a process for preparing a conjugate of a S. aureus type 5 or type 8 capsular polysaccharide and a carrier molecule, comprising the steps of: (a) depolymerizing the capsular polysaccharide, to give a polysaccharide fragment; (b) oxidizing the fragment in order to introduce an aldehyde group into at least one saccharide residue in the fragment, to give an oxidized saccharide residue; and (c) coupling the oxidized saccharide residue to a carrier molecule via the aldehyde group, thereby giving the conjugate. The coupling in step (c) may be direct, or may be via a linker molecule. The invention also provides a conjugate obtained or obtainable by this process.

Abstract: Novel enzymes, processes and antigenic structures useful in producing vaccines and compounds useful in combating gram-negative bacteria are described. Enzymes were isolated from the slime mold Dictyostelium discoideum and used to specifically degrade lipopolysaccharide (LPS). Enzymatic degradation permits residues of the LPS molecule, including immunogenic epitopes of the core oligosaccharide portion of the LPS, to remain unmodified during this enzymatic removal of fatty acids from the lipid A region of the LPS molecule.

Abstract: The present invention relates to the field of vaccines for protecting against polio, and in particular to combination vaccines for protecting against polio, diphtheria, tetanus, and pertussis diseases. Specifically, vaccines comprising reduced dose inactivated poliovirus are provided.

Abstract: Provided herein are vaccine vectors including an antigenic polypeptide and an HMGB1 polypeptide present on the surface of the vaccine vector. Compositions comprising the vaccine vectors are also provided and include a pharmaceutically acceptable carrier, suitably a carrier for oral or nasal administration. Also provided are methods of enhancing immune responses, in particular antibody immune response and suitably an IgA response, by administering the vaccine vectors or compositions disclosed herein to a subject.

Abstract: The present invention is directed to a bioconjugate vaccine, such as an O1-bioconjugate vaccine, comprising: a protein carrier comprising a protein carrier containing at least one consensus sequence, D/E-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline; at least one antigenic polysaccharide from at least one pathogenic bacterium, linked to the protein carrier; and, optionally, an adjuvant. In another aspect, the present invention is directed to a method of producing an O1-bioconjugate in a bioreactor comprising a number steps.

Abstract: The present invention relates to methods of reducing flocculation in an immunogenic composition, where said immunogenic composition comprises (a) Haemophilus influenzae B capsular polysaccharide or oligosaccharide (PRP) and (b) at least one non-PRP antigen. The invention further relates to kits comprising (i) a first composition comprising a Haemophilus influenzae B capsular polysaccharide or oligosaccharide (PRP) and a polyanionic polymer, and (ii) a second composition comprising a non-PRP antigen adsorbed onto an adjuvant with a zero point charge greater than 8.

Abstract: The present application describes a process for conjugating a PNAG which is less than 40% N-acetylated to a carrier protein.

Abstract: The present invention encompasses a novel S. aureus bioconjugate vaccine. More generally, the invention is directed to Gram-positive and other bioconjugate vaccines containing a protein carrier, at least one polysaccharide such as a capsular Gram-positive polysaccharide, and, optionally, an adjuvant or pharmaceutically acceptable carrier. The instant invention also includes methods of producing Gram-positive and other bioconjugate vaccines. An N-glycosylated protein is also provided that contains one or more polysaccharides such as Gram-positive polysaccharides. The invention is additionally directed to engineered prokaryotic organisms comprising nucleotide sequences encoding a glycosyltransferase of a first prokaryotic organism and a glycosyltransferase of a second prokaryotic organism. The invention further includes plasmids and prokaryotic cells transformed with plasmids encoding polysaccharides and enzymes which produce an N-glycosylated protein and/or bioconjugate vaccine.

Abstract: The present invention relates to the field of bacterial polysaccharide antigen vaccines. In particular, the present invention relates to bacterial polysaccharides conjugated to protein D from H. influenzae.

Abstract: Provided are immunogenic compositions and methods for eliciting an immune response against B. anthracis and other bacteria that contain 3-methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides. Conjugates of 3-methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides elicit an effective immune response against B. anthracis spores in mammalian hosts to which the conjugates are administered.

Abstract: The present invention relates to methods and compositions for treatment of microbial infections and for the enhancement of resistance to infection. The invention comprises administration of an effective amount of bacterial lysate compositions for the treatment of pathological conditions of microbial infections. The present invention can also be used to enhance the immune system to prevent infections by the administration of an effective amount of the compositions.

Abstract: The invention provides immunogenic polysaccharide protein conjugates comprising capsular polysaccharides from N. Meningitidis serogroup X and methods for preparation thereof. The present invention relates to N. meningitidis X saccharide-carrier protein conjugates prepared by a conjugation reaction. Accordingly, the instant invention relates to multivalent meningococcal polysaccharide protein conjugate composition comprising capsular saccharide from serogroups X and at least one capsular saccharide from A, C, W135 and Y wherein, i) polysaccharides A C W135 X are sized mechanically whereas polysaccharide Y is sized chemically, ii) all saccharide are conjugated to carrier protein via a linker with a cyanylation conjugation chemistry iii) all saccharide to protein ratios in final conjugates are between 0.2-0.6 and iv) at least two different carrier proteins selected from the group consisting of TT, DT and CRM197 are utilized.

Abstract: Methods and compositions pertaining to botulinum neurotoxin (BoNT) light chain epitopes are provided. In particular, the methods and compositions relate to the use of real and mimetic BoNT light chain epitopes for generating an immune response in a subject, and for immunization against BoNT toxicity. Methods and compositions for detecting, isolating, and purifying BoNT epitopes and anti-BoNT antibodies are also provided.

Abstract: A shortened process for producing a solution containing substantially purified capsular polysaccharides from a cellular Streptococcus pneumoniae lysate broth is described. Ultrafiltering and diafiltering a clarified S. pneumoniae lysate followed by pH adjustment to less than 4.5, preferably about 3.5, precipitated at least 98% of the protein in the solution without seriously affecting polysaccharide yield. Furthermore, following ultrafiltration and diafiltration and acidification to a pH of less than 4.5, filtration using activated carbon precipitated at least 90% of remaining protein without seriously affecting polysaccharide yield. Exemplary, non-limiting S. pneumoniae serotypes that can be purified using the shortened process of the invention are 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.

Abstract: The invention relates to a recombinant protein used for immunoprophylaxis of human Helicobacter pylori infection and a degradable slow-releasing microsphere-encapsulated oral vaccine preparation prepared from the same, and the preparation method thereof. Said recombinant protein is composed of A2 subunit and B subunit of the LT of enterotoxigenic Escherichia coli and urease B subunit. The vaccine provided in the invention used in human Helicobacter pylori infection is safe and effective and convenient for oral intake.

Abstract: The present invention is directed to a bioconjugate vaccine, such as an O1-bioconjugate vaccine, comprising: a protein carrier comprising a protein carrier containing at least one consensus sequence, D/E-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline; at least one antigenic polysaccharide from at least one pathogenic bacterium, linked to the protein carrier; and, optionally, an adjuvant. In another aspect, the present invention is directed to a method of producing an O1-bioconjugate in a bioreactor comprising a number steps.

Abstract: Nanoparticles for providing immune responses for the treatment or prophylaxis of infection by infectious agents such as viruses, parasites, bacteria, prions and fungi are described which comprises a core including metal and/or semiconductor atoms, wherein the core is covalently linked to a plurality of ligands, the ligands including a carbohydrate residue capable of stimulating an innate immune response, a T cell helper peptide and a danger signal. This platform may then be adapted by including one or more further ligands capable of producing a specific response to a target infectious agent.

Abstract: An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection. Also described is a method for making an immunogenic conjugate comprising Streptococcus pneumoniae serotype 1 polysaccharide covalently linked to a carrier protein, the method including partial de-O-acetylation of the polysaccharide by mild hydrolysis in an alkaline pH buffer.

Abstract: An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.

Abstract: The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, PREVNAR 13 (Pneumococcal 13-valent Conjugate Vaccine).

Abstract: A method is provided for covalently linking carbohydrates, proteins, nucleic acids, and other biomolecules under neutral conditions, using a Diels-Alder cycloaddition reaction. In an example, activated carbon-carbon double bonds were attached to free amino sites of a carrier protein, and a conjugated diene was attached to a carbohydrate hapten. Spontaneous coupling of the carbohydrate and the protein components under very mild conditions provided glycoconjugates containing up to 37 carbohydrate hapten units per carrier protein molecule. The method is also applicable to the immobilization of biomolecules on gel or solid supports. The conjugated products are useful as immunogens and as analytical and diagnostic reagents.

Abstract: The present invention relates to immunogenic compositions, comprising polypeptides and polysaccharides from Staphylococcus aureus. The present invention also relates to immunogenic compositions, comprising Staphylococcus aureus capsule polysaccharides conjugated to a carrier protein. In addition, the invention relates to methods of inducing an immune response in subjects against Staphylococcus aureus using immunogenic compositions of the Staphylococcus aureus polypeptides and capsule polysaccharides.

Abstract: The present invention is related to antigen from Chlamydia trachomatis which are recognized by specific antibodies from individuals infected with Chlamydia or which can induce T cells from the same individuals to secrete gamma-interferon. The T cell reactive antigens are present in a whole-cell lysate and have apparent molecular weights of 5-12, 16-20, 25-35 and 58-74 kDa as determined by SDS-PAGE. The antigens of the invention are believed to be useful in vaccines but also as diagnostic compositions.

Abstract: The present invention relates to the provision of immunogens comprising an antigenic PCSK9 peptide linked to an immunogenic carrier for the prevention, treatment or alleviation of PCSK9-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositing thereof and their use in medicine.

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 provides compositions and methods for stimulating an immune response using cationic lipids alone or in combination with antigens.

Abstract: The present invention relates to the use of alpha (2) macroglobulin complexes isolated from the serum of a mammal. The invention also relates to methods for making such complexes and compositions comprising alpha (2) macroglobulin complexes, isolated from the serum of a mammal, wherein such compositions are used in methods for the treatment and prevention of cancer and infectious disease. The invention also relates to methods for treating and preventing cancer and infectious disease using such complexes comprising, isolated from the serum of a mammal. The invention also encompasses methods for production of alpha (2) macroglobulin complexes.

Abstract: Methods of immunizing older adult subjects against Streptococcus pneumoniae infection are provided. Provided methods comprise immunization of naïve adult subjects with a conjugated pneumococcal polysaccharide vaccine. Optionally, initial immunization may be followed by additional immunization doses comprising conjugated pneumococcal polysaccharide vaccine or unconjugated pneumococcal polysaccharide vaccine composition.

Abstract: The invention relates to generation and use of cellular and humoral responses for the prevention and treatment of P. gingivalis related conditions and diseases.

Abstract: Disclosed are novel methods and compositions for combating diseases characterized by deposition of amyloid. The methods generally rely on immunization against amyloid precursor protein (APP) or beta amyloid (A?). Immunization is preferably effected by administration of analogs of autologous APP or A?, said analogs being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred as an immunogen is autologous A? which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes. Such methods and means include methods for the preparation of analogs and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

Abstract: An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.

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 application discloses a method for making an immunogenic composition comprising an improved way of conducting saccharide-protein conjugation reactions using carbodiimide condensation chemistry. Depending on the nature of the saccharide or protein carrier involved, the quality of the conjugate may be improved by adding one of the reaction components slowly to the reaction mixture. In addition, the conjugate is mixed with a staphylococcal antigen. Immunogenic compositions are further provided comprising the saccharide-protein conjugates made by the methods disclosed.

Abstract: When preparing HBsAg for use in a combination vaccine, it is known to add a non-ionic detergent after the HBsAg has been purified. Adding detergents after purification of HBsAg is not optimal, however, as it requires a separate processing step during manufacture. Thus the invention uses them during HBsAg purification.

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: Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

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: 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: An immunogenic composition comprising a siderophore covalently linked to a pharmaceutically acceptable carrier molecule wherein the antigenicity of the siderophore moiety is sufficient to stimulate an immunologic response to the siderophore when the composition is circulating in the bloodstream of a human or non-human animal and vaccine.

Abstract: The disclosure relates to a composition added to animal feed used in combination with a vaccine to enhance the effectiveness of the vaccine. Amongst other effects, the composition raises the titer of antibodies to the vaccine.

Abstract: Formulations of and dosing protocols for the administration of botulinum toxin that maximize efficacy and specificity while minimizing the likelihood of overdosing and undesirable side effects of treatment. The formulations include positively charged carriers, such as cationic peptides, which otherwise have no inherent botulinum-toxin-like activity. The dosing regimen is based on the pattern, quantity, and location of neuromuscular junctions in the target tissue. Because the number of neuromuscular junctions in a target tissue remains generally stable throughout life and because the pharmacological effect of botulinum toxin is localized at the neuromuscular junction, dosing efficacy is unaffected by muscle mass, age of the patient, or body weight.

Abstract: Capsular saccharides derived from serogroups W135 and Y of Neisseria meningitidis have altered levels of O-acetylation at the 7 and 9 positions of their sialic acid residues, and can be used to make immunogenic compositions. Relative to unmodified native saccharides, derivatives of the invention are preferentially selected during conjugation to carrier proteins, and conjugates of the derivatives show improved immunogenicity compared to native polysaccharides.

Abstract: An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.

Abstract: Methods of immunizing older adult subjects against Streptococcus pneumoniae infection are provided. Provided methods comprise immunization of naïve adult subjects with a conjugated pneumococcal polysaccharide vaccine. Optionally, initial immunization may be followed by additional immunization doses comprising conjugated pneumococcal polysaccharide vaccine or unconjugated pneumococcal polysaccharide vaccine composition.

Abstract: Methods for preparing an oligosaccharide-protein carrier immunogenic conjugate or a polysaccharide-protein carrier immunogenic conjugate. The methods include obtaining an oligosaccharide or polysaccharide having a KDO moiety located at the terminal reducing end of the oligosaccharide or polysaccharide that includes a carbonyl functional group; and reacting the carbonyl functional group of the KDO moiety with an aminooxylated protein carrier molecule resulting in a conjugate that includes a covalent oxime bond between the oligosaccharide and the protein carrier or the polysaccharide and the protein carrier.

Abstract: The invention provides compositions and kits comprising: (a) a saccharide antigen conjugated to a carrier; and (b) an alpha-glycosylceramide adjuvant. The invention further provides uses of the compositions. It has been found that suppression of anti-saccharide immune responses by alpha-glycosylceramides can be reversed by conjugating the saccharide to a carrier.

Abstract: The present invention relates to a composition comprising a) a B subunit of Shiga toxin or a functional equivalent thereof which is able to bind the Gb3 receptor, complexed with an antigen and b) at least one ligand of CDl capable of stimulating NK T cells; and to a pharmaceutical composition and a medicament comprising said composition.