Abstract: A novel recombinant chimera of DNA construct having esat-6 region of Mycobacterium tuberculosis and kinesin region of Leishmania donovani cloned together on two sides of self cleaving peptide in a DNA vaccine vector pVAX-1 wherein the chimeric construct is operatively linked to a transcriptional promoter thus capable of self replication and expression within the mammalian cell, and the process of preparation thereof comprising: analysis of the predicted protein sequence of kinesin motor domain and esat-6 domain using Promiscuous MHC Class-1 Binding Peptide Prediction Servers; amplification of gene coding for kinesin motor domain and esat-6 domain; cloning of kinesin esat-6 gene region in pGEM-T™ vector for sequence analysis; generation of chimeric construct by directional cloning in pVAX-1 vector.

Abstract: The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of the tuberculosis complex (M. tuberculosis, M. Bovis, M. africanum, M. microti). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from M. tuberculosis, the units of the fusion polypeptide being M. tuberculosis antigens. Further, the invention is related to the use of a vaccine comprising a fusion polypeptide sequence or nucleic acid sequence of the invention given at the same time as BCG, either mixed with BCG or administered separately at different sites or routes for preparing said immunogenic composition, vaccine, or pharmaceutical composition.

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: An isolated microorganism belonging to the genus Mycobacterium, having one or both of an inactivated gene Rv0757 that confers a PhoP? phenotype and an inactivated second gene which prevents the production of DIM (DIM? phenotype). Methods of making the microorganism, related pharmaceutical formulations and vaccines are also provided, as are related methods of treatment and vaccination. The pharmaceutical formulation may also serve as a vector or adjuvant.

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 present invention provides novel immunotherapeutic compositions and methods useful for treating or preventing microbial infections, weakened immune systems, diseases in which cells have become obligately anerobic and cellular proliferative disorders including cancer. The immunotherapeutics herein use benzaldehyde derivatives, precursors and intermediaries alone or in combination with additional therapeutic agents to stimulate the immune system and inhibit cellular proliferation.

Abstract: The invention relates to a novel adjuvant Mycobacterium w and or its constituents and adjuvant containing composition, which contains antigen(s) with pharmaceutical acceptable carrier and its uses. Mycobacterium w and or its constituents when administered with antigen(s) to mammal results in enhanced immunogenicity of antigen. The enhanced immunogenicity manifests as humoral responses as well as cell mediated immunity. The adjuvant effect is seen with variety of antigens in various mammals irrespective of their immune status at the time of administration of Mycobacterium w and antigen containing composition. e.g. immune naïve or preimmunized status.

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 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 provides vaccine compositions and methods for using the same. Generally, the vaccine is used to prevent infection of a microorganism that produces an HIF inducing compound. Accordingly, vaccines of the invention comprise at least a portion of an HIF inducing compound that is produced by the microorganism.

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 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 a strain of M. bovis BCG or M. microti, wherein said strain has integrated part or all of the RD1 region responsible for enhanced immunogenicity of the tubercle bacilli, especially the ESAT-6 and CFP-10 genes. These strains will be referred as the M. bovis BCG::RD1 or M. microti::RD1 strains and are useful as a new improved vaccine for preventing tuberculosis and as a therapeutical product enhancing the stimulation of the immune system for the treatment of bladder cancer.

Abstract: Provided are peptide vaccines including the signal peptide domain of selected target antigens of intracellular pathogens. The peptide vaccines of the invention contain multiple class II and class I-restricted epitopes and are recognized and presented by the majority of the vaccinated human population. Further provided, in particular, are anti tuberculosis vaccines. Also further provided are compositions including the vaccines as well as their use to treat or prevent infection.

Abstract: Recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses are disclosed. The recombinant molecules are comprised by at least one targeting unit and at least one antigenic unit connected through a dimerization motif. Also disclosed are nucleic acid molecules encoding the recombinant antibody-based molecule and methods of treating multiple myeloma or lymphoma in a patient using the recombinant antibody-based molecules or the nucleic acid molecules.

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 is directed to a method for promoting or stimulating a cell-mediated immune response to an antigen, by administering a target antigen (such as a protein) with a transport factor that contains a fragment of a bipartite protein exotoxin, but not the corresponding protective antigen. 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: Provided are mycobacteria deleted in at least a portion of a region 3 ESAT-6-like gene cluster. Also provided are mycobacteria comprising a mutation in an roc-1 gene. Additionally, vaccines comprising these mycobacteria are provided. Further provided are methods of making a recombinant mycobacterium, methods of inducing an immune response in a mammal, methods of inhibiting IL-12 production in a mammal, and methods of stimulating IL-12 production in a mammal. Vaccine adjuvants are also provided, as are methods of inducing immunity to a target antigen in a mammal.

Abstract: Tuberculosis (TB) is a major health problem and currently, the only licensed TB vaccine is Mycobacterium bovis Bacille Calmette-Guerin (M. bovis BCG). In the present invention, mutation of mycobacterial components reportedly involved in phagosome maturation inhibition was evaluated for vaccine purposes, as such mutations should result in better vaccine antigen processing and presentation. Thus, BCG mutants in genes coding for ManLAM capping ?-1,2-mannosyltransferases and the PI3P phosphatase SapM were evaluated as TB vaccines in a stringent mouse model. Vaccination with both ManLAM capping mutants and the SapM mutant resulted in significantly longer survival as compared to non-vaccinated mice, whereas vaccination with the parental BCG did not. Moreover, mice vaccinated with the SapM mutant survived significantly longer than mice vaccinated with the parental BCG.

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: Immunogenic compositions comprising growth regulatable recombinant attenuated intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens are provided. Exemplary immunogenic compositions include, growth regulatable and growth limited recombinant attenuated intracellular pathogen immunogenic compositions.

Abstract: A method of detecting an immune response to a paratuberculosis-specific antigen, comprising incubating a sample from a subject with the paratuberculosis-specific antigen and detecting the presence of an antibody in the sample as an indication of an immune response to the paratuberculosis-specific antigen. The antigen may be obtained from a novel M. paratuberculosis strain JTC303. The antigen may be obtained from the JTC303 culture filtrate. Also provided are antibodies to the paratuberculosis-specific antigen, and a diagnostic kit for the detection of an immune response to a paratuberculosis-specific antigen in a mammal.

Abstract: The invention relates to process for the preparation of formulations comprising a microorganism Mycobacterium w for the management of bronchial Asthma (obstructive lung disease).

Abstract: The present invention relates to a method of producing rough strains of a bacterium, such as Mycobacterium obuense, said method comprising exposing said bacterium to a sulfone and/or sulfonamide (such as 4,4?-Diaminodiphenyl sulfone or an analogue thereof). A rough strain of Mycobacterium obuense producible by said method and uses thereof. In particular, uses of a rough strain of Mycobacterium obuense deposited under the Budapest Treaty at the NCTC with the accession number NCTC 13365.

Abstract: The present invention relates to molecules, which can be used to induce a therapeutic or prophylactic immune response against MAP.

Abstract: The present invention relates to fusion proteins containing at least two Mycobacterium tuberculosis antigens. In particular, it relates to bi-fusion proteins which contain two individual M. tuberculosis antigens, tri-fusion proteins which contain three M. tuberculosis antigens, tetra-fusion proteins which contain four M. tuberculosis antigens, and penta-fusion proteins which contain five M. tuberculosis antigens, and methods for their use in the diagnosis, treatment and prevention of tuberculosis infection.

Abstract: Therapeutic vaccines comprising polypeptides expressed during the latent stage of mycobacteria infection are provided, as are multiphase vaccines, and methods for treating and preventing tuberculosis.

Abstract: Systems, methods, and compositions for a diagnostic method for detecting TB in non-human primates that is easy to use, sensitive, and specific. The method utilizes recombinant mycobacterial antigens, such as polyfusion proteins. The method utilizes an antigen-antibody-antigen arrangement to detect TB infection in nonhuman primates. The method can detect IgM antibodies to TB, in addition to IgG antibodies, providing ability to detect TB earlier in nonhuman primate TB infection as compared to conventional TB tests.

Abstract: The present invention provides live, attenuated Mycoplasma bacteria that exhibit reduced expression of one or more proteins selected from the group consisting of pyruvate dehydrogenase, phosphopyruvate hydratase, 2-deoxyribose-5-phosphate aldolase, and ribosomal protein L35, relative to a wild-type Mycoplasma bacterium of the same species. Also provided are vaccines and vaccination methods involving the use of the live, attenuated Mycoplasma bacteria, and methods for making live attenuated Mycoplasma bacteria.

Abstract: The present invention discloses a vaccine or immunogenic composition that can be administered to latently infected individuals to prevent reactivation of latent tuberculosis infection caused by species of the tuberculosis complex microorganisms (Mycobacterium tuberculosis, M. bovis, M. africanum). The invention is base on a number of M. tuberculosis derived proteins and protein fragments which are constitutively expressed in different stages of the infection. The invention is directed to the use of these polypeptides, immunologically active fragments thereof and the genes encoding them for immunological compositions such as vaccines.

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 inventive subject matter relates to a method for detecting the presence of a biological substance of interest in a test sample of saliva or oral fluid, comprising combining said test sample with a fluorescence-labeled ligand to said biological substance and detecting a change in the fluorescence polarization of said test sample produced by binding of said fluorescence-labeled ligand to said biological substance. In one aspect of the inventive subject matter, said method comprises additional steps for comparing the fluorescence polarization of said test sample with the fluorescence polarization of a control solution. Also provided is a miniaturized, portable apparatus for measuring the fluorescence polarization of a liquid sample.

Abstract: The present invention relates to compositions and fusion proteins containing at least two Mycobacterium sp. antigens, and nucleic acids encoding such compositions and fusion proteins. The compositions of the invention increase serological sensitivity of sera from individuals infected with tuberculosis, and methods for their use in the diagnosis, treatment, and prevention of tuberculosis infection.

Abstract: The present invention relates to compositions and fusion proteins containing at least two Mycobacterium sp. antigens, and nucleic acids encoding such compositions and fusion proteins. The compositions of the invention increase serological sensitivity of sera from individuals infected with tuberculosis, and methods for their use in the diagnosis, treatment, and prevention of tuberculosis infection.

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: A convenient way of inducing a broad recognition of dominant and subdominant responses to epitopes of any given antigen of importance for prophylaxis or treatment of a chronic disease is provided. The method involves by immunizing with pools of overlapping fragments (synthetic peptides, e.g., 10-30 mers with 2-20 aa overlap) of the desired antigen in appropriate adjuvants. The T cell repertoire is primed to include not only the immunodominant epitope recognized when the intact molecule is used for immunization and induced by the chronic infection itself, but induce a much broader and balanced response to a number of the subdominant epitopes as well. The vaccination with peptide mix induces a T-cell response that includes response to subdominant epitopes is important for protection against chronic disease that on their own induces a response focused only on immunodominant epitopes.

Abstract: The invention provides a method of diagnosing Mycobacterium tuberculosis infection in a human, or of determining whether a human has been exposed to Mycobacterium tuberculosis, comprising: (i) contacting T-cells from said human with one or more of (a) a peptide having the sequence shown in SEQ ID NO: 1; (b) a peptide having or comprising the sequence of at least 8 consecutive amino acids of the sequence shown in SEQ ID NO: 1; or (c) a peptide having or comprising a sequence which is capable of binding to a T-cell receptor which recognizes a peptide as defined in (a) or (b); and (ii) determining whether any of the said T-cells recognize said peptide, wherein steps (i) and (ii) are optionally carried out in vitro.

Abstract: Provided are mycobacteria comprising (a) a mutation that is not in a SecA2 gene that attenuates the virulence of the mycobacteria in a mammalian host, and (b) a mutation in a SecA2 gene that eliminates SecA2 activity. Also provided are mycobacteria that comprise a mutation in a SecA2 gene that eliminates SecA2 activity, where the mycobacteria are not Mycobacterium tuberculosis or Mycobacterium smegmatis. Additionally provided are methods of inducing an immune response in a mammal and methods of inducing an immune response to a pathogenic mycobacterium in a human using the above mycobacterial mutants.

Abstract: The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of the tuberculosis complex (M. tuberculosis, M. Bovis, M. africanum, M. microti). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from M. tuberculosis, the units of the fusion polypeptide being M. tuberculosis antigens. Further, the invention is related to the use of a vaccine comprising a fusion polypeptide sequence or nucleic acid sequence of the invention given at the same time as BCG, either mixed with BCG or administered separately at different sites or routes for preparing said immunogenic composition, vaccine, or pharmaceutical composition.

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: In one aspect, a method of treating cancer in a mammal is provided. The method comprises administering to the mammal an oncolytic vector that expresses a tumour antigen to which the mammal has a pre-existing immunity. In another aspect, a method of boosting immune response in a mammal having a pre-existing immunity to an antigen is provided comprising intravenous administration to the mammal of a B-cell infecting vector that expresses the antigen.

Abstract: The invention relates to a novel adjuvant Mycobacterium w and or its constituents and adjuvant containing composition, which contains antigen (s) with pharmaceutical acceptable carrier and its uses. Mycobacterium w and or its constituents when administered with antigen (s) to mammal results in enhanced immunogenicity of antigen. The enhanced immunogenicity manifests as humoral responses as well as cell mediated immunity. The adjuvant effect is seen with variety of antigens in various mammals irrespective of their immune status at the time of administration of Mycobacterium w and antigen containing composition. e.g. immune naïve or preimmunised status.

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: Methods of treating a mammal that is deficient in CD4+ and/or CD8+ lymphocytes are provided. The methods comprise inoculating the mammal with an attenuated mycobacterium in the M. tuberculosis complex. In these methods, the mycobacterium comprises two deletions, wherein a virulent mycobacterium in the M. tuberculosis complex having either deletion exhibits attenuated virulence. Use of these mycobacteria for the manufacture of a medicament for the treatment of mammals deficient in CD4+ and/or CD8+ lymphocytes is also provided.

Abstract: Compounds and methods for inducing protective immunity against tuberculosis are disclosed. The compounds provided include polypeptides that contain at least one immunogenic portion of one or more M. tuberculosis proteins and DNA molecules encoding such polypeptides. Such compounds may be formulated into vaccines and/or pharmaceutical compositions for immunization against M. tuberculosis infection, or may be used for the diagnosis of tuberculosis.

Abstract: The current invention relates to the diagnosis and treatment of diseases resulting from infections by Mycobacterium avium subsp. paratuberculosis. In particular the invention relates to the use of an antigen selected among (a) a synthetic peptide 5P having the following formula: DPhe-NMeVal-Ile-Phe-Ala-OMe (SEQ ID NO: 1); (b) a lipopeptide L5P consisting of the synthetic peptide a) wherein the N-terminal phenylalanine residue is N-acylated with an eicosanoic acid acyl chain; (c) a variant of peptide a) or lipopeptide b) able to react with anti-Mycobacterium paratuberculosis antibodies; for in vitro detection or quantification of specific anti-Mycobacterium paratuberculosis antibodies in a biological sample.

Abstract: The present invention provides novel immunotherapeutic compositions and methods useful for treating or preventing microbial infections, weakened immune systems, diseases in which cells have become obligately anerobic and cellular proliferative disorders including cancer. The immunotherapeutics herein use benzaldehyde derivatives, precursors and intermediaries alone or in combination with additional therapeutic agents to stimulate the immune system and inhibit cellular proliferation.

Abstract: The present invention provides novel immunotherapeutic compositions and methods useful for treating or preventing microbial infections, weakened immune systems, diseases in which cells have become obligately anaerobic and cellular proliferative disorders including cancer. The immunotherapeutics herein use benzaldehyde derivatives, precursors and intermediaries alone or in combination with additional therapeutic agents to stimulate the immune system and inhibit cellular proliferation.

Abstract: The present invention relates to peptide antigens of SEQ ID Nos. 1 to 10; repeat motif Gly-X-Gly-Asn-X-Gly of SEQ ID No. 11; and a method of developing drug against tuberculosis, said method comprising steps of targeting the proposed drug towards peptide antigens of SEQ ID Nos. 1 to 11, and thereby developing the drug against tuberculosis.

Abstract: The present invention is based on the identification and characterization of a number of novel M. tuberculosis derived proteins and protein fragments. The invention is directed to the polypeptides and immunologically active fragments thereof, the genes encoding them, immunological compositions such as diagnostic reagents containing the polypeptides.