The present invention relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding PD-L1. In particular, the present invention relates to said attenuated strain of Salmonella for use in the treatment of cancer.

Disclosed is the attenuated Salmonella typhi vaccine Ty21a utilized as a vector for Shigella and/or enterotoxogenic E. coli genes stably integrated in the Ty21a chromosome. These genes include a heterologous Shigella sonnei O-antigen biosynthetic gene region that comprises the wzz gene and expresses Shigella sonnei form 1 O-antigen, as well as a heterologous acid resistance biosynthetic gene system comprising a YbaS gene, which enables increased stability of the Ty21a vector at pH 2.5 relative to Ty21a without the integrated acid resistance biosynthetic gene system.

Antibody molecule-drag conjugates (ADCs) that specifically bind to lipopolysaceharides (LPS) are disclosed. The antibody molecule-drug conjugates can be used to treat, prevent, and/or diagnose bacterial infections and related disorders.

The presently-disclosed subject matter relates to crosslinkers, compositions, and methods for trapping a target of interest on a substrate of interest. The methods may be used to inhibit and treat pathogen infection and provide contraception. The methods may be used to trap or separate particles and other substances. The subject matter further relates to methods of identifying and preparing optimal crosslinkers and methods for manipulating targets of interest.

The present invention relates to detecting serum anti-FadA antibodies in test samples from a patient. Additionally, aspects of the present invention provide the basis for detection of serum anti-FadA antibody levels from test samples and correlation with various conditions of clinical relevance.

The present invention provides compositions for delivering an active agent to an animal, comprising an active agent, a first coating, a second coating and a third coating. The active agent is coated with the first coating, the first coating is coated with the second coating, and the second coating is coated with the third coating. The active agent is in contact with the first coating, not the second or third coating. The first coating separates the active agent from the second coating while the second coating separates the first and third coatings. The first, second and third coatings are different from each other. Also provided are methods for making and using the compositions.

A composition comprising intact killed bacterial cells that contain a therapeutic nucleic acid, a drug or a functional nucleic acid is useful for targeted delivery to mammalian cells. The targeted delivery optionally employs bispecific ligands, comprising a first arm that carries specificity for a killed bacterial cell surface structure and a second arm that carries specificity for a mammalian cell surface receptor, to target killed bacterial cells to specific mammalian cells and to cause endocytosis of the killed bacterial cells by the mammalian cells. Alternatively, the delivery method exploits the natural ability of phagocytic mammalian cells to engulf killed bacterial cells without the use of bispecific ligands.

The present invention relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding a VEGF receptor protein, for use in the treatment of cancer, wherein the treatment further comprises the administration of at least one further anti-cancer agent. The present invention further relates to a pharmaceutical composition comprising an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding a VEGF receptor protein, wherein the pharmaceutical composition further comprises at least one further attenuated strain of Salmonella comprising at least one copy of a further DNA molecule comprising a further expression cassette encoding a tumor antigen or a tumor stroma antigen.

The invention provides for an isolated antibody that specifically recognizes an epitope of the lipopolysaccharide (LPS) O3b-antigen structure of Klebsiella pneumoniae, which is a O3b-epitope incorporated in O3b-antigen comprising the structure of Formula (I), including one or more O3b-antigen mannose homopolymer repeating units, wherein MeP is methyl phosphate; and n is 0-50. The invention further provides for a pharmaceutical or diagnostic preparation comprising said antibody, and a method of producing said antibody.

本发明公开了种辐抗肽或其突变蛋白的制备和纯化方法，该方法可显著提高蛋白的纯度，便于工业化生产。本发明还提供了种辐抗肽突变蛋白，该突变蛋白是在辐抗肽蛋白CBLB502的基础上，将ND1和CD1结构域之间的氨基酸序列进行替换，所述突变蛋白具有SEQ ID NO:2所示的氨基酸序列，其稳定性显著优于现有技术中的CBLB502蛋白。

本发明公开了肠炎沙门菌sufB基因缺失株的构建方法，以及肠炎沙门菌sufB基因缺失能够降低肠炎沙门菌的毒力，且肠炎沙门菌sufB基因缺失能够应用于肠炎沙门菌疫苗。本发明利用Red同源重组方法构建肠炎沙门菌sufB基因缺失株，并对其生物学特性和毒力进行研究，明确了sufB基因缺失引起肠炎沙门菌毒力下降，为设计肠炎沙门菌疫苗靶点提供参考，进而防治肠炎沙门菌感染，同时能够进步探索肠炎沙门菌SufB蛋白的生理学功能。

A composition is provided for detecting a Salmonella microorganism in sample. The composition comprises at least one first selective agent that inhibits the growth of Gram-positive microorganisms, a first differential indicator system comprising at least one first differential indicator compound that is converted to a first detectable product by a Salmonella microorganism, and a second differential indicator system comprising a second differential indicator compound that is converted by urease enzyme activity to a second detectable product. Optionally, the composition may comprise a third differential indicator system comprising a third differential indicator compound that is converted by a beta -galactosidase enzyme activity to a third detectable product. Methods of using the composition to detect a Salmonella microorganism are also provided.

Antibody molecule-drag conjugates (ADCs) that specifically bind to lipopolysaceharides (LPS) are disclosed. The antibody molecule-drug conjugates can be used to treat, prevent, and/or diagnose bacterial infections and related disorders.

Provided is a marker for determining a mental disease, which can be used for an objective diagnosis of a mental disease. A marker for determining a metal disease, which comprises at least one enterobacterium selected from those belonging to Bifidobacterium, Lactobacillus, Lactobacillus brevis, Lactobacillus reuteri subgroup, Lactobacillus sakei subgroup, Atopobium cluster, Bacteroides fragilis group, Enterococcus, Clostridium coccoides group, Clostridium leptum subgroup, Staphylococcus, Clostridium perfringens and Enterobacteriaceae.

Provided is a composition effective for salmonella-related infection. The discovery was made that the Bacillus amyloliquefaciens strain is effective on Salmonella typhimethylium which is a causative bacterium of salmonella-related infection.

The present invention relates to detecting serum anti-FadA antibodies in test samples from a patient. Additionally, aspects of the present invention provide the basis for detection of serum anti-FadA antibody levels from test samples and correlation with various conditions of clinical relevance.

The present invention relates to novel methods of diagnosing, preventing, and treating diseases, disorders, and infections relating to T-cell response. The disclosed methods for predicting MHC class II epitopes that elicit CD4+ T-cell response are N based on the three-dimensional protein structure of an antigen of interest. Given such an antigen, structural properties of the protein taken from experimental and modeling data are used to compute an epitope likelihood score that characterizes the location of epitopes likely to elicit an immune response to CD4+ T-cells. The epitopes are then used to construct biomolecules, including peptides, which may be used to diagnose, prevent, and/or treat a number of diseases, disorders, and infections.

The present invention provides cell-targeting molecules which can deliver a CD8+ T-cell epitope cargo to the MHC class I presentation pathway of the cell. The cell-targeting molecules of the invention can be used to deliver virtually any CD8+ T-cell epitope from an extracellular space to the MHC class I pathway of a target cell, which may be a malignant cell and/or non-immune cell. The target cell can then display on a cell-surface the delivered CD8+ T-cell epitope complexed with MHC I molecule. The cell-targeting molecules of the invention have uses which include the targeted labeling and/or killing of specific cell-types within a mixture of cell-types, including within a chordate, as well as the stimulation of beneficial immune responses. The cell-targeting molecules of the invention have uses, e.g., in the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections.

[0081] The present invention relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding a VEGF receptor protein for use in cancer immunotherapy, wherein the cancer is characterized by VEGF receptor protein expressing cancer cells. The present invention further relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding a VEGF receptor protein for use in cancer immunotherapy, wherein the cancer is characterized by VEGF receptor protein expressing cancer cells, and wherein the cancer is selected from the group consisting of glioblastoma, carcinoid cancer, kidney cancer, particularly renal cell carcinoma, thyroid cancer, lung cancer, particularly Non-Small Cell Lung Cancer (NSCLC), breast cancer, ovarian cancer, prostate cancer, gastrointestinal cancer, particularly colorectal cancer, more particularly colon cancer, and skin cancer, particularly melanoma. The present invention further relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding a VEGF receptor protein for use in cancer immunotherapy in a patient comprising at least one VEGF receptor protein expressing cancer cell.

Methods using chemotherapy drugs promote targeting of S. typhimurium A1-R of melanoma, thereby enhancing efficacy against the melanoma PDOX. A metastatic melanoma obtained from the right chest wall of a patient was previously established orthotopically in the right chest wall of nude mice as a patient-derived orthotopic xenograft (PDOX) model. We previously showed that the combination of tumor targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and chemotherapy was highly effective against the melanoma PDOX. In the present study, we investigated the mechanism of the high efficacy of this combination. Combination therapy significantly increases S. typhimurium A1-R tumor targeting alone (S. typhimurium A1-R+TEM: p<0.01, S. typhimurium A1-R+VEM: p<0.01).

Provided herein are genetically modified microbes. In one embodiment, a genetically modified microbe includes an exogenous polynucleotide that includes a pheromone-responsive region. In one embodiment, the pheromone-responsive region is derived from a conjugative plasmid from a member of the genus Enterococcus spp. The pheromone-responsive region includes a pheromone-responsive promoter and an operably linked coding region encoding an antimicrobial peptide. In one embodiment, a genetically modified microbe includes an exogenous polynucleotide that includes a promoter and an operably linked coding sequence encoding an antimicrobial peptide, where expression of the coding region is controlled by a modulator polypeptide and is altered by a modulating agent, and where the coding region encodes an antimicrobial peptide. Also provided herein are methods of using the genetically modified microbes, including methods for inhibiting growth of an Enterococcus spp., a pathogenic E. coli, or a pathogenic Salmonella spp., for treating a subject, and for modifying a subject's gastrointestinal microflora.

A human or humanized monoclonal IgG antibody (mAb) specifically recognizing the D-galactan-ll antigen of Klebsiella pneumoniae O1 which is characterized by a bactericidal CDC activity, its method of production, medical and diagnostic use.

本发明公开了ebgR基因敲除重组志贺氏菌的制备及应用。本发明提供了构建重组菌的方法，为抑制或沉默福氏志贺氏菌基因组上的ebgR基因表达，得到重组菌。本发明利用λRED同源重组的方法成功敲除了301中的ebgR基因，得到ebgR缺失株，并利用豚鼠角膜实验、III型分泌系统诱导分泌及小鼠肺竞争性侵袭三个毒力评价模型，初步断定其中ebgR基因缺失株的毒力有明显减弱，表明ebgR基因在志贺氏菌致病过程中有可能起到重要作用，得到的ebgR基因缺失株可以用作减毒疫苗的制备。

The present invention refers to pharmaceutical products comprising immunogenic compositions for modulating the immune system, which therapeutically effective amount of a Immmological Response Shifter (IRS) comprising two or more immunoactive antigenic agents presenting pathogen-associated molecular patterns (PAMPS) and/or danger associated molecular patterns (DAMPS) and/or Stress Response Signals (SRS) in association with an antibiotic and one or more physiologically acceptable carriers, excipients, diluents or solvents. In other embodiments, the present invention refers to methods to treat severe bacterial infections, sepsis and modulating the immune system.

Devices and methods for the detection of antigens are disclosed. Devices and methods for detecting food-borne pathogens are disclosed.