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 present invention describes compositions for both diagnostic and therapeutic applications. In one embodiment, the present invention contemplates a method of identifying an active M. tuberculosis infection. In another embodiment, the present invention contemplates a method of monitoring a M. tuberculosis infection. In yet another embodiment, the present invention contemplates a method of monitoring a patient's response to treatment for an active M. tuberculosis infection. In a further embodiment, the present invention contemplates a method of monitoring a patient's response to treatment for an active M. tuberculosis infection.

Abstract: Compounds, particularly, glucopyranosyl lipid adjuvant (GLA) compounds, having the following structure (I) are provided: or a pharmaceutically acceptable salt thereof, wherein L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, Y1, Y2, Y3, Y4, R1, R2, R3, R4, R5, R6, are as defined herein. Pharmaceutical compositions, vaccine compositions, and related methods for inducing or enhancing immune responses, are also provided.

Abstract: The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.

Abstract: Provided herein are isolated polypeptides comprising the amino-terminal domain of Mycobacterium tuberculosis porin A (MtpA), wherein the polypeptide is a porin monomer. Also provided are isolated polypeptides comprising the carboxy-terminal domain of Mycobacterium tuberculosis porin A, wherein the polypeptide is a toxin. Also provided are methods of treating or preventing a Mycobacterium tuberculosis (Mtb) infection in a subject with or at risk of developing a Mtb infection. Further provided are chimeric porin polypeptides comprising a first polypeptide comprising an amino-terminal domain of Mycobacterium tuberculosis porin and a second polypeptide comprising an antigen and the use the chimeric porin polypeptides in methods of eliciting an immune response in a subject.

Abstract: Provided herein are methods and compositions for stabilization of active agents. The active agents are distributed, mixed or embedded in a silk fibroin matrix, thereby retaining the bioactivity of the active agents upon storage and/or transportation. In some embodiments, the storage-stable vaccine-silk compositions are also provided herein.

Abstract: The present disclosure provides a DNA molecule capable of replication in Mycobacteria having a nucleic acid sequence as disclosed in SEQ ID NO: 1, a shuttle vector constructed using it and a transformed cells containing the present vector. The vector of about 18 kb of the present disclosure contains 16 ORFs, a replication origin and a rep-like protein essential for replication. Therefore, the plasmid of the present disclosure can be utilized as a gene delivery system/research, and also in a therapeutic system such as immune therapeutics by effectively delivering proteins or heterologous DNA and expressing the encoded DNA in cells.

Abstract: Described herein is a mycobacterium mutant, comprising at least one mutation in at least one gene sequence encoding global gene regulators (GGRs) selected from the group consisting of sigH, sigL, sigE, ECF-1, and mixtures thereof, wherein the GGR gene is at least partially inactivated. Described herein also is a vaccine based on the mutant and a method of differentiating between subjects that have been infected with mycobacterium and subjects that have not been infected with mycobacterium or have been vaccinated with a mycobacterium vaccine.

Abstract: The present invention is directed to heat shock proteins from Mycobacterium leprae as well as their encoding polynucleotides and vectors and host cells containing these polynucleotides. These heat shock proteins and their encoding polynucleotides are useful in detection of Mycobacterium leprae. In addition, the heat shock protein can be used as an adjuvant in a pharmaceutical composition containing an antigen to induce or enhance the immune response against the antigen. Further, the heat shock protein may be used to treat atopic conditions or as a vaccine against Mycobacterium leprae. Alternatively, the heat shock protein can be used to form a fusion protein with an antigen to induce or enhance the immune response against the antigen.

Abstract: The present invention relates to combination vaccines and/or the combined use of immunogenic compositions for the treatment and/or prophylaxis of cattle against microbiological infections, wherein the infections are caused by M. bovis and at least one further cattle relevant pathogen. The combination vaccine as described herein comprises at least one M. bovis antigen, preferably the attenuated, avirulent M. bovis as provided herewith and one or more further immunologically active components effective for the treatment and/or prophylaxis of infections caused by a further pathogen of cattle.

Abstract: The present invention describes compositions for both diagnostic and therapeutic applications. In one embodiment, the present invention contemplates a method of identifying an active M. tuberculosis infection. In another embodiment, the present invention contemplates a method of monitoring a M. tuberculosis infection. In yet another embodiment, the present invention contemplates a method of monitoring a patient's response to treatment for an active M. tuberculosis infection. In a further embodiment, the present invention contemplates a method of monitoring a patient's response to treatment for an active M. tuberculosis infection.

Abstract: The present invention relates to, inter alia, a method of raising an immune response against a pathogen which comprises administering (i) one or more first immunogenic polypeptides derived from said pathogen; (ii) one or more adenoviral vectors comprising one or more heterologous polynucleotides encoding one or more second immunogenic polypeptides derived from said pathogen; and (iii) an adjuvant; wherein the one or more first immunogenic polypeptides, the one or more adenoviral vectors and the adjuvant are administered concomitantly. The invention also relates to vaccines, pharmaceutical compositions, kits and uses employing said polypeptides, adenoviral vectors and adjuvants.

Abstract: Particular aspects provide efficient allelic exchange methods to generate directed mutations within genes of slow-growing stains of mycobacteria (e.g., Mycobacterium avium subsp. paratuberculosis (Map), Map 10 or GFP-expressing Map K-10) using a phage-delivery system, and demonstrate high efficiency allelic exchange. Additional exemplary aspects provide non-naturally occurring slow-growing strains of mycobacteria (e.g., Map, M. bovis, M. tuberculosis) having at least one gene deletion (e.g., pknG, relA, lsr2, panC, panD, proC, trpD, sapM (MAP3432), lysA_1, leuD, and leuC, and deletion mutants at the orthologous loci of two known virulence genes in pathogenic mycobacteria (relA and pknG) and one gene related to colony morphology and biofilm formation in fast growing mycobacteria (lsr2) were made. Further aspects provide novel vaccines comprising such deletion mutants, or portions thereof, and methods for making said vaccines. Yet further aspects provide methods for protecting a mammal from virulent Map, M.

Abstract: The invention relates to genes and proteins involved in the sporulation of Mycobacteria and the use thereof in the technical fields of immunology and medicine. A vaccine comprising spore forming peptides, such as CotA or CotD, or antibodies thereto is used for the treatment of diseases caused by Mycobacterium such as leprosy and tuberculosis.

Abstract: A vaccination method is provided. The method comprises administering to a mammal a histone deacytelase inhibitor in conjunction with a vaccine that expresses an antigen to which the mammal has a pre-existing immunity.

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 invention features methods for increasing or maintaining the number of functional cells of a predetermined type, for example, insulin producing cells of the pancreas, blood cells, spleen cells, brain cells, heart cells, vascular tissue cells, cells of the bile duct, or skin cells, in a mammal (e.g., a human patient) that has injured or damaged cells of the predetermined type.

Abstract: A method of assessing an intracellular pathogen infection and/or monitoring an intracellular pathogen infection in an individual comprises determining whether the individual has (a) T-cells that secrete IFN-? only, (b) T-cells that secrete IL-2 only or (c) T-cells that secrete both IFN-? and IL-2 in response to an intracellular pathogen antigen and optionally determining any change in this cytokine profile.

Abstract: The present invention is directed to a polypeptide which comprises: (i) an Rv2386c protein sequence; (ii) a variant of an Rv2386c protein sequence; or (iii) an immunogenic fragment of an Rv2386c protein sequence. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of tuberculosis.

Abstract: A method of preparing a compound of formula (III): (M)x-(S)y-(M?)z??(III) wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M? is independently a mycolic acid residue including a ?-hydroxy acid moiety and each S is a monosaccharide unit; the method comprising reacting one or more mycolic acids with one or more saccharide units wherein the hydroxyl group of each ?-hydroxy acid moiety is protected prior to reaction with the one or more saccharide units.

Abstract: A composition and method for immunizing a mammal infected with Mycobacterium are disclosed. The genes gcpE, pstA, kdpC, papA2, impA, umaA1, fabG2_2, aceAB, mbtH2, lpqP, map0834c, cspB, lipN, and map1634 of M. paratuberculosis and the products that they encode are vaccine targets for Johne's and Crohn's disease. Eighteen M. paratuberculosis-specific genomic islands (MAPs) were identified. Three inverted large genomic fragments in M. paratuberculosis (INV) were also identified. These genomic identifiers represent novel virulence determinants that can be used as targets for vaccines and for developments of drugs against Johne's disease. The methods can be used to deliver an immunizing compound to a mammal, to provide an immune response against Johne's or Crohn's disease in the mammal.

Abstract: The present invention relates to novel bacterial and mycobacterial compositions containing RNA and cell walls, and methods for making and using these compositions. These compositions have immune stimulating and anti-cancer activity.

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: A vaccine is provided wherein a polypeptide or combination of peptides from M. tuberculosis is administered to a subject to elicit an immune response. The polypeptide vaccine is administered as part of a prime-boost strategy with BCG vaccine to increase the immunoprotection in a subject such that prevention or elimination of disease is achieved. Finally, a pharmaceutical package is provided that encompasses a polypeptide vaccine for M. tuberculosis that when administered to a subject elicits immunoprotection.

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: The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Abstract: Serum antibody assays capable of distinguishing cases of inactive TB from cases of active TB include a combination of at least three M. tuberculosis protein antigens, at least one for which a positive response is consistent with inactive TB and antigens, and at least one for which a negative response is consistent with inactive TB.

Abstract: Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response.

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: There is provided a diagnostic reagent for use in the detection of M. bovis or M. tuberculosis infection in an animal, comprising a peptide which has an epitope from Mycobacterium bovis hypothetic protein Mb3645c (SEQ ID NO: 1) or an epitope from a polypeptide having at least 76% identity with SEQ ID NO: 1.

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: Provided herein are Mycobacterium smegmatis porin nanopores, systems that comprise these nanopores, and methods of using and making these nanopores. Such nanopores may be wild-type MspA porins, mutant MspA porins, wild-type MspA paralog porins, wild-type MspA homolog porins, mutant MspA paralog porins, mutant MspA homolog porins, or single-chain Msp porins. Also provided are bacterial strains capable of inducible Msp porin expression.

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: Disclosed are therapeutic methods for ex-vivo activation of immune cells from a cancer patient for the purpose of inducing tumor regression and/or suppressing metastasis and/or tumor recurrence. In one embodiment mononuclear cells of a patient are isolated from peripheral blood and activated by a combination of innate immune system activators together with means allowing for T cell activation.

Abstract: The present invention relates to the use of live mycobacterium of the M. tuberculosis complex for preparing a medicament, wherein the function of the zmp1-gene is inactivated, pharmaceutical compositions prepared from such mycobacteria as well as a method for the treatment and/or prophylaxis of a disease or medical condition using said pharmaceutical composition.

Abstract: Disclosed are methods and compositions for treating or preventing microbial infections.

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

Abstract: The 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 invention is directed to proteins expressed by Mycobacterium tuberculosis and not by BCG and their use as diagnostic reagents.

Abstract: The present invention relates to M. tuberculosis proteins and peptides, and subsequences, portions or modifications thereof and methods and compounds comprising the same for eliciting, stimulating, inducing, promoting, increasing, or enhancing an anti-M. tuberculosis immune response in a subject.

Abstract: The present invention relates to a method of preventing, treating or inhibiting the development of tumors or metastases in a subject and to an immunomodulator for use in such therapy, in combination with a chemotherapeutic agent. An aspect the present invention is a method of preventing, treating, reducing, inhibiting and/or controlling the formation or establishment of metastasis of a primary neoplasia, tumor or cancer at one or more sites distinct from a primary neoplasia, tumor or cancer, in a subject intended to undergo chemotherapy, wherein the method comprises administering to the subject, a therapeutically effective amount of an antimetabolite pyrimidine analogue and an immunomodulator.

Abstract: A method of assaying for peptide-specific T-cells comprises adding peptide to a fluid sample of fresh peripheral blood mononuclear cells, and detecting a cytokine such as interferon-? produced by T-cells that have been pre-sensitized to the peptide. The assay method is quick and cheap and is expected to be useful for the study of various disease states including Hepatitis B, Hepatitis C, tuberculosis, malaria, HIV and influenza.

Abstract: The invention relates to a recombinant Mycobacterium cell for use as a vaccine.

Abstract: The present invention relates to vaccine(s) comprising cancer cells expressing antigen(s), excipients, optionally adjuvant wherein the said antigen(s) is expressed on contacting the said cancer cell with p38 inducer, for use in treatment of Cancer. The vaccine composition induces specific immune response against homologous and heterologus cancer cells of the tissue/organ. The invention also provides method of preparing the same.

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: A method for metabolomically evaluating a subject's response to an anti-mycobacterial agent. The method includes the steps of generating multiple small molecule profiles using samples collected from the subject at or immediately prior to the start of treatment and at a times subsequent to the start of treatment with the anti-mycobacterial agent, identifying predetermined biomarkers in the small molecule profiles of the subject and comparing to a known standard established for the agent as an indication of whether the human is benefiting from treatment with the agent. Also provided are methods of monitoring treatment compliance, methods for establishing biomarkers indicative of treatment efficacy and validated biomarkers shown to be effective in assessing efficacy of anti-tuberculosis drugs.

Abstract: Immunogenic compositions comprising an Rv1196 related antigen, wherein the conductivity of the composition is 13 mS/cm or lower, or the concentration of salts of the composition is 130 mM or lower, and their use in medicine, are provided.

Abstract: Provided is a pharmaceutical composition that includes one or more inactivated Mycobacterium spp., which are preferably inactivated using gamma irradiation, and which is than 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: The present invention relates to a pharmaceutical vaccine composition comprising: (a) a pathogen-derived antigen selected from the group consisting of Mycobacterium tuberculosis antigen, Bacillus anthracis antigen, HAV (hepatitis A virus) antigen, HBV (hepatitis B virus) antigen, HCV (hepatitis C virus) antigen, HIV (human immunodeficiency virus) antigen, influenza virus antigen, HSV (herpes simplex virus) antigen, Hib (Haemophilus influenzae type b) antigen, Neisseria meningitidis antigen, Corynebacterium diphtheriae antigen, Bordetella pertussis antigen, Clostridium tetani antigen and Varicella virus antigen; (b) a deacylated non-toxic LOS (lipooligosaccharide); and (c) a pharmaceutically acceptable carrier.

Abstract: The invention relates to a method for immunising a subject against Mycobacterium tuberculosis ox Mycobacterium bovis. The method comprises parenterally administering to the subject an immunologically effective amount of a first antigen from the Mycobacterium or a first polynucleotide encoding the first antigen and administering to the lung of the subject an immunologically effective amount of a second antigen from the Mycobacterium or a second polynucleotide encoding the second antigen. The two administration steps are carried out less than four weeks apart. The invention also relates to a kit for carrying out the method of the invention.