Abstract: The invention provides compositions and methods for preventing a metabolic disorder or bacterial infection in a subject, the composition comprising a bacterial endotoxin.

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: Described are acellular pertussis (aP) vaccine compositions comprising Bordetella pertussis antigens pertussis toxoid (PT), filamentous hemagglutinin (FHA), and fimbriae types 2 and 3 (FIM), and optionally pertactin (PRN), wherein FIM is present in an amount of 12-100 ?g per human dose.

Abstract: The present invention relates to chimeric protein vaccines and methods of use thereof in the treatment of Staphylococcus aureus. One embodiment of the present invention provides a method of generating an immune response in a mammal, that includes administering to the mammal, a composition having a chimeric protein having at least one of: a portion of a cholera toxin, a portion of a heat-labile toxin, and a portion of a shiga toxin; and an antigen having at least one of: an antigenic material from S. aureus and an antigenic material from a S. aureus-specific polypeptide.

Abstract: The invention relates to a method for determining the quantity of pre-synaptic neuromuscular blocking substance (notably botulinum toxin) contained in a sample. In one aspects, the method comprises the following steps: (i) determining the minimum voltage Vm needed to induce the contraction of muscle tissue, said muscle tissue being connected to an electrical stimulator through a motor nerve and preferably immersed in an oxygenated physiological buffer containing glucose; (ii) adding the sample containing the pre-synaptic neuromuscular blocking substance; (iii) electrically stimulating, at a voltage at least equal to Vm, the muscle tissue at certain time intervals; (iv) comparing the effect induced by the sample to the effect induced by a reference substance and thereby determining the quantity of the pre-synaptic neuromuscular blocking substance in the sample.

Abstract: Disclosed are a highly efficient method for production of heterologous proteins performed by utilizing microorganisms, as well as fusion proteins, and an antiserum. The method includes a method for production of a protein (A) in the form of a fusion protein, comprising the steps of (a) preparing a DNA which codes for a fusion protein comprising the peptide chain forming the protein (A) and the C-terminal peptide or its fragment (B) of the Cry proteins produced by Bacillus thuringiensis, and (b) introducing the DNA into a host bacterium to transform the same, and (c) allowing the fusion protein to be expressed in the transformed host bacterium, as well as a method for production of the protein (A) itself comprising a further step of removing the peptide chain (B) from the fusion protein obtained.

Abstract: The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

Abstract: The disclosure pertains to conjugates of the capsular polysaccharide of Vibrio cholerae O139, or a structurally and/or immunologically related oligo- or poly-saccharide, and a carrier. These conjugates are useful as pharmaceutical compositions and/or vaccines to induce serum antibodies which have bactericidal (vibriocidal) activity against V. cholerae, in particular V. cholerae O139, and are useful to prevent, treat and/or reduce the severity of disease caused by V. cholerae infection, such as cholera. The present disclosure also relates to diagnostic tests for V. cholerae infection, and/or cholera caused by V. cholerae infection, using one or more of the oligo- or poly-saccharide-carrier conjugates or antibodies described above.

Abstract: The present invention concerns an universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein: STxB is the Shiga Toxin B subunit or a functional equivalent thereof, Z is an amino-acid devoided of sulfhydryl group, n being 0, 1 or a polypeptide, Cys is the amino-acid Cysteine, and the use thereof for MHC class I and MHC class II presentation of antigens.

Abstract: Vaccines for conferring immunity in mammals to infective pathogens are provided, as well as vectors and methods for plastid transformation of plants to produce protective antigens and vaccines for oral delivery. The invention further provides transformed plastids having the ability to survive selection in both the light and the dark, at different developmental stages by using genes coding for two different enzymes capable of detoxifying the same selectable marker, driven by regulatory signals that are functional in proplastids as well as in mature chloroplasts. The invention utilizes antibiotic-free selectable markers to provide edible vaccines for conferring immunity to a mammal against Bacillus anthracis, as well as Yersina pestis. The vaccines are operative by parenteral administration as well. The invention also extends to the transformed plants, plant parts, and seeds and progeny thereof. The invention is applicable to monocot and dicot plants.

Abstract: A method for preserving a polypeptide comprising: (a) providing an aqueous solution of (i) the polypeptide, (ii) one or more sugars, and (iii) a compound of formula (I) or a physiologically acceptable salt or ester thereof and/or a compound of formula (II) or a physiologically acceptable salt or ester thereof; and (b) drying the solution to form a composition incorporating the polypeptide.

Abstract: A bacterial toxin protein such as a Shiga toxin protein is efficiently produced using plant cells. The plant cells are transformed using a DNA construct containing DNA encoding a hybrid protein in which the bacterial toxin proteins such as the Shiga toxin proteins are tandemly linked through a peptide having the following characteristics (A) and (B) to produce the bacterial toxin protein in the plant cells: (A) a number of amino acids is 12 to 30; and (B) a content of proline is 20 to 35%.

Abstract: A chimeric Shiga toxoid according to the invention contains an enzymatically-inactivated StxA subunit and a native StxB subunit. This hybrid Shiga toxoid induces the production of broadly cross-reactive species of antibodies against Shiga toxin following immunization. The StxA subunit is modified so that it is enzymatically inactive. The invention thus encompasses the Shiga toxoid or fragments thereof and the nucleic acid sequence of the Shiga toxoid or fragments thereof. The invention further encompasses the production of a Shiga toxoid, the production of antibodies using the Shiga toxoid and methods of productions, and an immunogenic composition containing the Shiga toxoid.

Abstract: The present invention relates to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.

Abstract: Chromatographic processes and systems for purifying a botulinum toxin from an APF fermentation medium.

Abstract: The present invention relates to chimeric protein vaccines and methods of use thereof in the treatment of Staphylococcus aureus. One embodiment of the present invention provides a method of generating an immune response in a mammal, that includes administering to the mammal, a composition having a chimeric protein having at least one of: a portion of a cholera toxin, a portion of a heat-labile toxin, and a portion of a shiga toxin; and an antigen having at least one of an antigenic material from S. aureus and an antigenic material from a S. aureus-specific polypeptide.

Abstract: Methods of using tetanus toxin to modulate or control neural functions or nonneural cellular activities at selected sites in animals, particularly in mammals, and more particularly in humans, are provided. Pharmaceutical formulations to modulate neural functions or non-neural cellular activities of an animal at selected sites in animals, particularly in mammals, and more particularly in humans are also provided. Uses of tetanus toxin in preparation of medicaments for methods of treating clinical disorders or symptoms of animals, particularly mammals and more particularly humans are also provided.

Abstract: The invention provides compositions comprising liposomes, an antigen capable of inducing a humoral immune response, a carrier comprising a continuous phase of a hydrophobic substance, and an adjuvant that activates or increases the activity of TLR2. The invention also provides uses for such compositions in inducing a humoral response and methods for their use in the treatment of a disease, disorder or ailment ameliorated by a humoral immune response.

Abstract: The present invention is drawn to the nucleic and amino acid sequences encoding vaginolysin (VLY) toxin from Gardnerella vaginalis, and biologically active fragments and variants thereof. The invention is also directed to anti-VLY antibodies and to their use therapeutically and in a new ELISA assay of VLY toxin. Other embodiments of the invention are directed to VLY toxoids and to vaccines that use the new VLY toxoids as immunogens.

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: The present invention relates to at least one botulinum neurotoxin for treatment of prevention of pain associated with diabetic neuropathy wherein said botulinum neurotoxin is prepared for local administration, wherein the local administration is not in the central nervous system (CNS), and wherein pain is treated at a site distant to the site of administration.

Abstract: Cysteine-specific radiolabeled Cry1Fa protein retains insecticidal activity against insect pests and binds to insect brush border membrane vesicle receptors in a saturable manner. The biologically-active radiolabeled Cry1Fa protein is useful in competitive binding assays with other Cry toxins.

Abstract: A liposomal composition, preferably a vaccine, comprising liposomes formed of liposome forming compounds, containing coentrapped polysaccharide antigen and T-cell dependent protein carrier, such as tetanus toxoid or diphtheria toxin modified to render it non-toxic. The invention is of use in the production of vaccines against Haemophilus influenzae, Streptococcus pneumoniae or Neisseria meningitidis.

Abstract: Methods for treating obsessions and compulsions by local administration of a Clostridial toxin. The obsessions or compulsions can be eye poking, body rocking, finger biting, counting, checking and related disorders treated by low dose, intramuscular administration of a botulinum toxin.

Abstract: A method for treating a patient having ulcerative colitis, by administering a drug which containing an effective amount of tetracyclines is provided. The drug may also contain penicillins and/or metronidazoles.

Abstract: The invention is a method for reducing the symptoms of vertigo. The method is performed by delivering a therapeutically effective amount of presynaptic neurotoxin, such as Botulinum Toxin A, in a pharmaceutically safe form to suitable locations around the head and neck.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

Abstract: A method of controlling dysregulation of the dorsal cutaneous nerve of the clitoris and, in particular, a method for treating PGAD is provided. In one aspect, the method comprises administering a neurotoxin, such as a botulinum toxin, to the clitoral area of the human in need of treatment.

Abstract: Disclosed herein are methods of using extracellular matrix digesting enzymes and neurotoxins, such as a Clostridial neurotoxins, to treat various medical conditions, such as overactive bladder, benign prostatic hyperplasia, hyperhidrosis, for example.

Abstract: Infraorbital dark circles can be treated by administration of a botulinum toxin to a patient. The botulinum toxin can be botulinum toxin type A and the botulinum toxin can be administered to or to the vicinity of an eye of a patient with infraorbital dark circles.

Abstract: The present invention provides methods and compositions for the stimulation of immune responses. In particular, the present invention provides immunogenic nanoemulsion compositions and methods of using the same for the induction of immune responses (e.g., innate and/or adaptive immune responses (e.g., for generation of host immunity against a bacterial species of the genus Streptococcus (e.g., Streptococcus pneumoniae))). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

Abstract: The present invention pertains to an antigenic formulation comprising a biological antigen, wherein the formulation comprises an oil containing as a principle constituent a fatty acid ester of eleostearic acid. The invention also pertains to the use of the said oil to manufacture an antigenic formulation.

Abstract: The present invention pertains to pharmaceutical compositions which comprise a botulinum neurotoxin from Clostridium botulinum, the neurotoxin being free of the complexing proteins naturally present in the botulinum neurotoxin complex or being chemically modified or being modified by genetic manipulation. Moreover the pharmaceutical compositions of the instant invention have good stability and are advantageously formulated free of human serum albumin.

Abstract: For the first time, an O-specific polysaccharide antigen that is a Shigella Sonnei, phase I, exopolysaccharide has been produced and characterized, said exopolysaccharide being an authentic natural compound in the form of a bacterial capsular polysaccharide. The exopolysaccharide contains a non-toxic lipid component, namely non-hydroxylated fatty acids, and exhibits low pyrogenicity and high immunogenicity. Effective, highly specific and safe vaccines for the prophylaxis and/or treatment of Shigella sonnei shigellosis are developed on the basis of the above-mentioned exopolysaccharide, as well as pharmaceutical compositions with a broad spectrum of action, in particular, in modulating immune response.

Abstract: A Clostridial toxin pharmaceutical composition comprising a Clostridial toxin, such as a botulinum toxin, wherein the Clostridial toxin present in the pharmaceutical composition is stabilized by a non-protein excipient such as a polyvinylpyrrolidone, a disaccharides, a trisaccharide, a polysaccharide, an alcohol, a metal, an amino acid, a surfactant and/or a polyethylene glycol.

Abstract: A novel dosing regimen for the administration of botulinum toxin 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: The invention provides a diphtheria, tetanus and pertussis vaccine comprising a low dose of each of diphtheria toxoid (D), tetanus toxoid (T), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (69K). The vaccine maintains an ability to prevent pertussis while showing exceptionally low reactogenicity. Combination vaccines comprising additional antigens are also provided.

Abstract: The present disclosure relates to vaccine compositions and methods of using the vaccine compositions to provide protection against various Gram-negative bacterial infections, including Burkholderia infections.

Abstract: It is disclosed here that synaptotagmin I (syt I) and synaptotagmin II (syt II) are the cellular receptors for botulinum neurotoxin B (BoNT/B) that mediate the cellular entry and toxicity of BoNT/B. The BoNT/B binding domains of syt I and II are also disclosed. While syt I needs gangliosides for BoNT/B binding, syt II can bind to BoNT/B in the absence of gangliosides. Various nucleic acids and polypeptides that relate to the BoNT/B binding domain of syt I or II are disclosed. Further disclosed are methods of reducing BoNT/B toxicity, methods of identifying agents that can block the binding between BoNT/B and syt I or II, methods of identifying agents that can bind to the BoNT/B binding domain of syt I or II, methods of detecting BoNT/B or Clostridium botulinum and kits for use thereof.

Abstract: The present invention utilizes patient-specific landmarks in order to treat headache pain. In one aspect, the present invention relates to the administration of Clostridial toxins, such as a botulinum neurotoxin, to a patient suffering from a headache pain, where the location of administration of the botulinum toxin is based upon at least one suture line of the patient's skull.

Abstract: Antibodies that specifically bind to toxins of C. difficile, antigen binding portions thereof, and methods of making and using the antibodies and antigen binding portions thereof are provided herein.

Abstract: The application relates to Clostridium difficile cell surface polysaccharides, compositions comprising Clostridium difficile cell surface polysaccharides, and includes kits, methods and uses thereof.

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: This invention relates to novel compositions of botulinum toxin that can be applied topically for various therapeutic, aesthetic and/or cosmetic purposes. The compositions may include botulinum toxin complexes, wherein the amounts of hemagglutinin, non-toxin non-hemagglutinin and/or exogenous albumin are selectively and independently reduced compared to conventional commercially available botulinum toxin. The compositions may further contain molecules that are not native to botulinum toxin and that bind non-covalently to the botulinum toxin complexes, thereby acting as skin-tropic “adhesion molecules” to improve the ability of the toxin complexes to adhere to and to penetrate the skin epithelium. The compositions have an improved safety profile compared to existing botulinum-containing compositions that are injected subcutaneously. Methods for the use of such compositions are also contemplated by this invention.

Abstract: Vaccination with the combination of Ag85B-TB10.4 and IC31® adjuvant generated a high amount of polyfunctional CD4+T cells expressing high levels of IFN-?, TNF-?, and IL-2. This in turn led to significant protection against infection with M. tuberculosis in the mouse aerosol challenge model of tuberculosis. Both the immunogenicity of the vaccine and its ability to protect against TB infection was highly dependent on the antigen dose. Thus, whereas the standard antigen dose of 5 ?g, as well as 15 ?g, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 ?g increased both the immunogenicity of the vaccine as well as its protective efficacy to a level comparable to that observed in BCG vaccinated mice. Thus, the IC31® adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

Abstract: It refers to a recombinant alpha-hemolysin polypeptide of Staphylococcus aureus, comprising a deletion in the stem domain, wherein at least one heterologous sequence is inserted in a region selected from the group consisting of regions defined by amino acid position of 108 to 151, 1 to 5, 288 to 293, 43 to 48, 235 to 240, 92 to 97, 31 to 36,or 156 to 161 of SEQ ID NO: 1, with the proviso that, if the heterologous sequence contains five or more consecutive histidines the moiety of the heterologous sequence other than the moiety of five or more consecutive histidines has a minimum length of 11 amino acids; or a variant thereof comprising 1-50 amino acids added, substituted or deleted in SEQ ID NO. 1 and the activity to form oligomers and to bind to lipidic bilayers. It also provides a medicament and vaccine comprising said recombinant polypeptide.

Abstract: The invention relates to the isolation, characterization and expression of DNA fragments encoding sphingomyelinases D from three species of Loxosceles genus spiders, namely L. boneti., L. reclusa and L. laeta, and the toxoids thereof. The invention also relates to the production of active sphingomyelinases D and the toxoids thereof using recombinant means and to the use of same as an immunogen for the production in vertebrates of antibodies that neutralize the corresponding venom and the respective fragments F(ab?)2. The invention further relates to the use of recombinant sphingomyelinases D as part of an antigen matrix which can be used in the immunopurification of antibodies and the fragments thereof or as part of any diagnostic device used to obtain clinical confirmation that the causal agent of poisoning in a patient is a spider of the Loxosceles genus.