Abstract: Methods of Mycobacterial immunotherapy for the treatment of cancer are described. In certain cases, these methods concern administration of attenuated Mycobacteria by intradermal injection into non tumor tissues. Methods of the invention, provide safe and effective treatments for malignant tumors and the compositions for use in such treatments. Methods for determine the effectiveness of such immunotherapies are also described.

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 of inducing latency in Mycobacterium permits preparation of an in vitro model system of latent mycobacterial infection. Latency is induced in a pure culture of Mycobacterium by exposing it to multiple stress conditions, including a low nutrient culture medium without glycerol, a low pH, a relatively high level of carbon dioxide and a relatively low gas phase oxygen level. An in vitro model of mycobacterial infection employs macrophages induced from THP1 cells which are then infected with Mycobacterium. The infected macrophages are grown under hypoxic conditions to induce latency in the mycobacteria. The in vitro model of infection is useful in evaluating compounds for activity against latent mycobacteria.

Abstract: The present invention includes cold-adapted, acid-fast bacterium for use as a vaccine and a vaccine vector. In preferred embodiments, the cold-adapted, acid-fast bacterium is a Mycobacteria, for example, Mycobacteria shottsii.

Abstract: The present invention relates to novel recombinant vaccines providing protective immunity against tuberculosis. Further, the present invention refers to novel recombinant nucleic acid molecules, vectors containing said nucleic acid molecules, cells transformed with said nucleic acid molecules and polypeptides encoded by said nucleic acid molecules.

Abstract: The present invention provides a method for specifically detecting a Mycobacterium tuberculosis complex-specific secretory protein MPT64 antigen in a biological sample, whereby diagnosis of infection with Mycobacterium tuberculosis is carried out rapidly and safely with higher accuracy than before. An antibody that recognizes an epitope for MPB64 located in any one of amino acid sequences of SEQ ID NOS: 2 to 4, particularly a monoclonal antibody was obtained. Thus, an immunoassay using the antibody, particularly a sandwich immunoassay using first and second antibodies to MPB64, particularly an immunochromatographic assay and an immunochromatographic test strip are provided. A biological sample can be rapidly subjected to the immunoassay without culturing or after culturing for a time before Mycobacterium tuberculosis complex bacteria in the sample substantially start to grow.

Abstract: The present invention relates to a method of treating a subject for an infectious disease. This method involves selecting a subject infected with an infectious disease-causing agent. The infectious disease-causing agent elicits, in the selected subject, an immune response that is insufficient to cure the selected subject of the infectious disease. The method also involves administering to the selected subject a synthetic peptide representing an antigen epitope associated with an immune response to the infectious agent. The immune response to the synthetic peptide is sufficient to treat the selected subject for the infectious disease.

Abstract: The invention relates to the treatment of mycobacterial infections, autoimmune disorders, lymphoproliferative disorders and induction of immunosuppression following transplantation using coronin 1 and modulators of coronin 1. Particular modulators of coronin 1 are compounds which inhibit the production of coronin 1 or the formation of active coronin 1 from a coronin 1 precursor, partly or entirely inactivate coronin 1, inhibit concentration of coronin 1 at the site of T cell activation, or inhibit the coronin 1 mediated signaling pathway downstream of the T cell receptor. Examples of such modulators are antibody or antibody fragments, coronin 1 peptide fragments or corresponding phosphopeptides, or anti-sense oligonucleotides, e.g. siRNA or shRNA.

Abstract: Methods of preparing mutants of Mycobacterium tuberculosis with one or more disrupted genes are presented, where the disrupted genes include ctpV, rv0990c, rv0971c, and/or rv0348. Compositions containing mutants with attenuated virulence and pathogenesis, which are capable of stimulation of an immune response against tuberculosis, are described. Compositions and methods relating to immunogenic compositions, which include an attenuated M. tb strain in which the M. tb genome includes a disruption of at least one of the ctpV gene, the rv0990c gene, the rv0971c gene, and the rv0348 gene, are also provided.

Abstract: The present invention discloses a method for inhibiting the growth of Mycobacterium tuberculosis, comprising: administering at least one selective binding agent such as an anti-CD13 antibody or a CD13 antagonist which can bind a CD13 receptor of a cell to inhibit infection of Mycobacterium tuberculosis. Administration of anti-CD13 antibody can reduce an expression level of the CD13 receptor, inhibit entry of Mycobacterium tuberculosis into monocytes, reduce survival of Mycobacterium tuberculosis in monocytes, and kill Mycobacterium tuberculosis effectively.

Abstract: The present invention relates to a modified polypeptide with a biological activity to lyse cell walls of bacteria, wherein the polypeptide has no caspase, clostripain, enterokinase, factor Xa, granzyme B, staphylococcus peptidase I (V8 Protease), plasmin, streptopain, bacillolysin and/or thrombin cleavage site. The invention further relates to nucleic acids with a sequence encoding a polypeptide according to the present invention.

Abstract: Described is an immunostimulatory oligodeoxynucleic acid molecule (ODN) having the structure according to formula (I), wherein any NMP is a 2? deoxynucleoside monophosphate or monothiophosphate, selected from the group consisting of deoxyadenosine-, deoxyguanosine-, deoxyinosine-, deoxycytosine-, deoxyuridine-, deoxythymidine-, 2-methyl-deoxyinosine-, 5-methyl-deoxycytosine-, deoxypseudouridine-, deoxyribosepurine-, 2-amino-deoxyribosepurine-, -6-S-deoxyguanine-, 2-dimethyl-deoxyguanosine- or N-isopentenyl-deoxyadenosine-monophosphate or -monothiophosphate, NUC is a 2? deoxynucleoside, selected from the group consisting of deoxyadenosine-, deoxyguanosine-, deoxyinosine-, deoxycytosine-, deoxyuridine-, deoxythymidine-, 2-methyl-deoxyinosine-, 5-methyl-deoxycytosine-, deoxypseudouridine-, deoxyribosepurine-, 2-amino-deoxyribosepurine-, 6-S-deoxyguanine-, 2-dimethyl-deoxyguanosine- or N-isopentenyl-deoxyadenosine, any X is O or S, a and b are integers from 0 to 100 with the proviso that a+b is between 4 and 150,

Abstract: Whole-cell vaccines and methods for their use in producing protective immune responses in vertebrate hosts subsequently exposed to pathogenic bacteria. The present invention involves a method of enhancing antigen presentation by intracellular bacteria in a manner that improves vaccine efficacy. After identifying an enzyme that has an anti-apoptotic effect upon host cells infected by an intracellular microbe, the activity of the enzyme is reduced, thereby modifying the microbe so that it increases immunogenicity. Also, the present invention provides a method of incrementally modifying enzyme activity to produce incrementally attenuated mutants of the microbe from which an effective vaccine candidate can be selected.

Abstract: The invention provides a method for therapeutic treatment of a patient having active tuberculosis (TB), the method comprising: administering to the patient a recombinant adenovirus vector that comprises nucleic acid encoding the Ag85A, Ag85B and TB10.4 antigens of Mycobactium tuberculosis (Mtb). Advantageously, the method can be used to shorten conventional drug therapy for treating active TB.

Abstract: The present invention is directed to methods of preventing reactivation of active and latent M. tuberculosis infections by administering a pharmaceutical composition comprising a nucleic acid encoding a Mtb72f fusion protein, or a Mtb72f fusion protein or an immunogenic fragment thereof, for example together with an adjuvant. The Mtb72f nucleic acid or fusion protein can be administered with one or more chemotherapeutic agents effective against a M. tuberculosis infection. The methods also provide for shortening the time course of a chemotherapeutic regimen against a M. tuberculosis infection.

Abstract: The present invention discloses new antigens of Mycobacterium avium subsp. paratuberculosis, antigenic compositions comprising at least two of said antigens, as well as epitopes, antibodies or hypervariable fragments thereof and nucleotide sequences coding for them. The present invention also concerns their use in diagnosis and/or vaccination against Mycobacterium avium subsp. paratuberculosis, in mammals, and in particular in cattle, but also in sheep and caprines. The invention also concerns their potential application in diagnosis and/or vaccination against Crohn's disease in human.

Abstract: The invention relates to a combination vaccine against Mycobacterium avium subspecies paratuberculosis (MAP) and M. tuberculosis and/or M. bovis for use in methods of immunizing a subject against mycobacterial infection, preventing or treating mycobacterial infection, and preventing a disease associated with mycobacterial infection.

Abstract: The current invention relates to the field of Biotechnology applied to human health. Here it is described a vaccine vehicle wherein toxins from eukaryotic organisms are encapsulated into multilamellar vesicles obtained by the dehydration-rehydration procedure whose lipidic composition is dipalmitoylphosphatidylcholine:cholesterol in a 1:1 molar ratio for subcutaneous or intramuscular administration. These compositions do not require the use of other adjuvants. The disclosed compositions allow modulation of CTL-specific immune response against one or several antigens co-encapsulated into toxin-containing liposomes. The vaccinal vehicle of the present invention shows advantages over others disclosed by the previous art due to the robustness and functionality of the induced immune response as well as its immunomodulating properties.

Abstract: There is provided an antigenic composition comprising (a) a first mycobacterial antigenic polypeptide or a first mycobacterial polynucleotide; and (b) a second mycobacterial antigenic polypeptide or a second mycobacterial polynucleotide; wherein: (i) said first mycobacterial antigenic polypeptide comprises a polypeptide sequence having at least 70% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 1 or 7, or a fragment thereof having at least 7 consecutive amino acids thereof; (ii) said first mycobacterial polynucleotide comprises a polynucleotide sequence encoding said first mycobacterial antigenic polypeptide; (iii) said second mycobacterial antigenic polypeptide comprises a polypeptide sequence having at least 70% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 5, or a fragment thereof having at least 7 consecutive amino acids thereof; and (iv) said second mycobacterial polynucleotide comprises a polynucleotide sequence encoding said second mycobacterial polypeptid

Abstract: The present invention relates to the use of a therapeutically effective amount of abscisic acid (ABA) or its analogs to treat or prevent inflammation induced by exposure to lipopolysaccharide (LPS) or respiratory inflammation. The invention also relates to methods and composition for enhancing vaccine efficacy using ABA.

Abstract: The present invention relates to novel mycobacterial compositions containing RNA and cell walls, and methods for making and using these compositions. These compositions have immune stimulating and anti-cancer activity. The present invention also relates to a synthetic medium for the cultivation of mycobacteria.

Abstract: Methods for producing an immune response to Mycobacterium tuberculosis (Mtb) are disclosed herein. In several examples, the immune response is a protective immune response. In additional embodiments, methods are disclosed for preventing an infection with Mtb, or treating an infection with Mtb. Pharmaceutical compositions for the prevention and/or treatment of tuberculosis are also disclosed.

Abstract: The present invention provides a polynucleotide adjuvant (PICKCa) composition and methods of use in eliciting an immune response, in particular a mucosal immune response. The polynucleotide adjuvant comprises of a polyriboinosinic-polyribocytidylic acid (PIC), at least one antibiotic and at least one positive ion. The present invention also provides an immunogenic composition comprising the polynucleotide adjuvant composition together with other immunogenic compositions such as an antigen (e.g., as in a vaccine) selected from viral, bacterial, fungal, parasitic and/or cancer antigens. The present invention further contemplates methods of use of such adjuvant compositions, particularly in eliciting an immune response, in particular a mucosal immune response to an antigenic compound.

Abstract: The present invention provides a novel attenuated vaccine for tuberculosis. Furthermore, when used as a subcutaneous vaccine, the present invention induces a higher level of protection than the current vaccine. Finally, the present invention results in less tissue damage and a lower number of colony forming units (CFU) in the lungs compared to subjects vaccinated with BCG.

Abstract: Use of Mycobacterium bovis BCG killed by Extended Freeze Drying (EFD) for preventing or treating atherosclerosis.

Abstract: An adjuvant combination that stimulates immune activation or response includes a hydrophobic immune adjuvant and a pathogen derived lipoprotein that chaperones the hydrophobic immune adjuvant to an immune receptor.

Abstract: A method is provided for identifying mycobacterial genes that are induced or up-regulated under continuous culture conditions defined by a dissolved oxygen tension of up to 10% air saturation measured at 37° C. when compared with a dissolved oxygen tension of at least 40% air saturation measured at 37° C. Said induced or up-regulated genes form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said induced or up-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Abstract: This application relates to compositions comprising components prepared from Gram positive bacteria such as Gram positive facultative intracellular bacteria for treatment of disorders comprising an immune dysregulation in humans and animals.

Abstract: A method is provided for identifying mycobacterial genes that are induced or up-regulated under culture conditions that are nutrient-starving and which maintain mycobacterial latency, said conditions being obtainable by batch fermentation of a mycobacterium for at least 20 days post-inoculation, when compared with culture conditions that are not nutrient-starving and which support exponential growth of said mycobacterium. Said induced or up-regulated genes form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said induced or up-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Abstract: The present invention describes an immunogenic formulation to be used in mammals against the respiratory syncytial virus (RSV), consisting in the Calmette-Guérin bacillus (BCG) strain or other attenuated Mycobacterium strain that expresses heterologously at least one protein or immunogenic fragment of the RSV subtype A or RSV subtype B strains, originated from proteins NS1, NS2, N, P, M, SH, M2 (ORF1), M2 (ORF2), L, F or G. The genetic material that encodes for these proteins or immunogenic fragments is inserted into the BCG genome or extrachromosomally in one or several copies, which expression is regulated by endogenous or exogenous BCG promoters, either constitutive or inducible. The viral proteins or immunogenic fragments can be expressed by BCG as cytoplasmic-soluble, extracellularly-secreted or cell membrane-bound proteins. The preparation can further contain combinations of previously described formulations. The formulation can be stabilized by freeze-drying (conservation range from 4° C. and 25° C.

Abstract: Provided is a pharmaceutical composition that includes one or more inactivated Mycobacterium spp., which are preferably inactivated using gamma irradiation, and which is then formulated for mucosal or pulmonary delivery to a subject. The pharmaceutical compositions are useful for preventing or treating mycobacterium-associated infections in a subject, including a human subject.

Abstract: Provided are recombinant mycobacteria having a mutation in an nlaA gene or in a nuoG gene. Also provided are isolated and purified nlaA proteins and nuoG proteins from a mycobacterium. Additionally provided are isolated and purified nucleic acids comprising a recombinant nlaA gene or a recombinant nuoG gene. Further provided are methods of inducing an immune response in a mammal and methods of making a recombinant mycobacterium using the nlaA gene or the nuoG gene.

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

Abstract: Compounds and methods for diagnosing tuberculosis or for inducing protective immunity against tuberculosis are disclosed. The compounds provided include polypeptides that contain at least one immunogenic portion of one or more Mycobacterium proteins and DNA molecules encoding such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Mycobacterium infection in patients and biological samples. Antibodies directed against such polypeptides are also provided. In addition, such compounds may be formulated into vaccines and/or pharmaceutical compositions for immunization against Mycobacterium infection.

Abstract: Immunogenic compositions comprising recombinant intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens and immunostimulatory molecules are provided. Exemplary immunogenic compositions include, but are not limited to, recombinant BCG expressing Mycobacteria major extracellular proteins and immunostimulatory molecules.

Abstract: RP-factors, their cognate receptors, convertases, respective genes and inhibitors or mimetics thereof are described. In particular, antibodies, pharmaceutical compositions and (therapeutic, diagnostic) methods based on the RP-factors and their receptors/convertases are described.

Abstract: The present invention pertains to the use of a non-live carbohydrate containing composition, the carbohydrate being also found in live Lawsonia intracellularis cells in association with the outer cell membrane of these cells, for the manufacture of a vaccine for protection against an infection with Lawsonia intracellularis, the vaccine being in a form suitable for systemic administration.

Abstract: The invention provides a bioassay for detection of Mycobacterium tuberculosis infection comprising artificially modified peptide subsequences of the T-cell epitope from M. tuberculosis Ag85B. Particularly preferred peptides have the form: SGGNNSPAX (SEQ ID 26), where X is Methionine (SEQ ID 18), Leucine (SEQ ID 17), Alanine (SEQ ID 15) or Valine (SEQ ID 10) and NNSPAV (SEQ ID 14). The invention also provides peptides for use in such an assay.

Abstract: Methods of preparing mutants of Mycobacterium tuberculosis with one or more disrupted genes are presented, where the disrupted genes include ctpV, rv0990c, rv0971c, and/or rv0348. Compositions containing mutants with attenuated virulence and pathogenesis, which are capable of stimulation of an immune response against tuberculosis, are described. Compositions and methods relating to immunogenic compositions, which include an attenuated M. tb strain in which the M. tb genome includes a disruption of at least one of the ctpV gene, the rv0990c gene, the rv0971c gene, and the rv0348 gene, are also provided.

Abstract: A method for the treatment of myeloma and thymoma by administering a therapeutically effective dose of Mycobacterium indicus pranii with Cyclophosphamide. This disclosure generally relates to the field of cancer biology. More specifically, this disclosure relates to the immunotherapeutic treatment of myeloma and thymoma, using a combination of heat killed Mycobacterium indicus pranii and the widely administered chemotherapeutic drug, Cyclophosphamide. Mycobacterium indicus pranii has already shown its efficacy as an immunomodulator and has been safely administered to humans. The most common method of cancer management is the application of chemotherapeutic drugs which results in side-effects. At lower non-toxic doses Cyclophosphamide is not effective. The present disclosure discloses a method of improving efficacy of non-toxic doses of Cyclophosphamide by administrating it together with Mycobacterium indicus pranii. This disclosure is relevant for the treatment of other lymphomas as well.

Abstract: A vaccine against Mycobacteria tuberculosis (Mtb) is provided. The vaccine comprises a recombinant Bacille Calmette-Guerin (BCG) subunit-based vaccine in which one or more Mtb antigens and one or more Mtb resuscitation or reactivation antigens are overexpressed, and in which at least a portion of the DosR regulon is up-regulated. The vaccine is protective against active Mtb infection both pre- and post-exposure to Mtb, and thus prevents disease symptoms due to the recurrence of a latent Mtb infection.

Abstract: The present invention relates to an isolated microorganism belonging to the genus Mycobacterium, characterized in that it comprises inactivating the gene Rv0757 that confers a PhoP? phenotype and inactivating a second gene that prevents the production of DIM (DIM-phenotype). Additionally, the present invention comprises the use of said microorganism for producing a vaccine for immunizing against or preventing tuberculosis.

Abstract: The present disclosure provides improved compositions comprising rifabutin, clarithromycin, and clofazimine for use in the treatment of Inflammatory Bowel Diseases. In one instance, the compositions may comprise a formulation of rifabutin, clarithromycin, and clofazimine in a single dosage form, such as a capsule, tablet, etc., with one or more specific excipients.

Abstract: The invention discloses identification, method of making and therapeutic use of synthetic oligopeptides for the treatment of infectious diseases, in particular tuberculosis. The oligopeptides are designed using virulence mediating protein for Mycobacterium Tuberculosis bacteria. The antibodies may be used for diagnostic and treatment purposes of infectious diseases. In particular, the sequences with SEQ ID 1 to 11 may be used to produce such oligopeptides synthetically. Suppression of activity of mycobacterium tuberculosis may be achieved with oligopeptides analogous to SEQ ID 1 to 11 as a therapeutic drug and/or as a vaccine in a mammal.

Abstract: Mycobacterium w or its components are found to have poly TLR antagonistic activity to induced TLRs by varieties of TLR ligands. The induced TLR against which inhibitory effect is seen includes TLR 3, 4, 5, 6, 7, 8, 9. They also display antagonistic activities to effects of TLR ligands. They are also useful in management of diseases wherein TLRs are over expressed, like sepsis, multiple sclerosis, optic neuritis, Chronic obstructive pulmonary diseases multiple myeloma etc.

Abstract: The present invention is directed to a method for delivering exogenous proteins to the cytosol, by binding a target antigen (such as a protein) to a transport factor that contains a fragment of a bipartite protein exotoxin, but not the corresponding protective antigen. Preferably, the target antigen is fused to the transport factor. Preferred transport factors include the protective antigen binding domain of lethal factor (LFn) from B. anthracis, consisting of amino acids 1-255, preferably a fragment of at least 80 amino acids that shows at least 80% homology to LFn, and a fragment of about 105 amino acids from the carboxy portion that does not bind PA. The target antigen can include any molecule for which it would be desirable to elicit a CMI response, including viral antigens and tumor antigens.

Abstract: Contemplated compositions, devices, and methods are drawn to various antigens from the pathogen M. tuberculosis and their use in vaccines, therapeutic agents, and various diagnostic tests. In particularly preferred aspects, the antigens are immunodominant and have quantified and known relative reactivities with respect to sera of a population infected with the pathogen, and/or have a known association with a disease parameter.

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 invention concerns a methylated immunogenic recombinant peptide sequence comprising mycobacterial heparin-binding hemagglutinin. The invention also concerns chemical and enzymatic methods for preparing such a sequence, the sequence being previously produced in a non-methylated recombinant form then methylated by post-translational modification. The invention further concerns recombinant tools, vectors and host cells for implementing post-translational enzymatic methylation of the recombinant HBHA. The invention finally concerns immunogenic compositions comprising methylated, native or recombinant HBHA, such compositions being useful for preparing vaccines against mycobacterial infections.

Abstract: Whole-cell vaccines and methods for their use in producing protective immune responses in vertebrate hosts subsequently exposed to pathogenic bacteria. The present invention involves a method of enhancing antigen presentation by intracellular bacteria in a manner that improves vaccine efficacy. After identifying an enzyme that has an anti-apoptotic effect upon host cells infected by an intracellular microbe, the activity of the enzyme is reduced, thereby modifying the microbe so that it increases immunogenicity. Also, the present invention provides a method of incrementally modifying enzyme activity to produce incrementally attenuated mutants of the microbe from which an effective vaccine candidate can be selected.