Abstract: The present invention is directed to a fusion protein comprising a light chain region of a Clostridial neurotoxin and a heavy chain region of a Clostridial neurotoxin, where the light and heavy chain regions are linked by a disulfide bond. The fusion protein also has a single chain antibody positioned upstream of the light chain region, where the single chain antibody possesses antigen-binding activity. Also disclosed are therapeutic agents, treatment methods, propeptide fusions, isolated nucleic acid molecules, expression systems, host cells, and methods of expressing fusion proteins.

Abstract: Polyacrylamide (PAM)-coated nanosand that may be a relative permeability modifier (RPM) and that is applied to treat a wellbore in a subterranean formation. The treatment may be for excess water production. The PAM-coated nanosand is PAM-hydrogel-coated nanosand. The PAM-coated nanosand os nanosand coated with PAM hydrogel. The PAM hydrogel includes crosslinked PAM in water. Application of the PAM-coated nanosand may reduce water production from the subterranean formation into the wellbore. The PAM hydrogel of the PAM-coated nanosand may expand in a water zone of the subterranean formation to restrict water flow into the wellbore. The PAM hydrogel of the PAM-coated nanosand may contract in an oil zone of the subterranean formation so not to significantly restrict crude oil flow into the wellbore.

Abstract: The present invention relates to Neisseria ORF2086 proteins, crossreactive immunogenic proteins which can be isolated from nesserial strains or prepared recombinantly, including immunogenic portions thereof, biological equivalents thereof, antibodies that immunospecifically bind to the foregoing and nucleic acid sequences encoding each of the foregoing, as well as the use of same in immunogenic compositions that are effective against infection by Neisseria meningitidis serogroup B.

Abstract: The present invention relates to the preparation and use in primates of whole organismvaccines in which the MEP pathway is disrupted such that synthesis of HMBPP by the bacterial cells is substantially blocked. The data provided demonstrates that, when bacteria or other vaccine vectors that comprise an active MEP pathway are used in vaccine methods, the ?? T cell response dominates, potentially clearing the vaccine strain via ?? T cell-mediated killing of vector infected antigen presenting cells and reducing its utility as a stimulator of a productive adaptive immune response, specifically priming or boosting of CD4+ and CD8+ ?? T cell responses, specific for listerial-encoded antigens. By disrupting the MEP pathway, activation and expansion of ?? T cells is limited in the recipient primate, resulting in resulting in an increase in the magnitude and duration of inflammation and in the magnitude and duration of antigen presentation by the cellular vaccine.

Abstract: The present invention relates to the preparation and use in recipients of CAR-T cell-derived effector cells which are modified to limit their proliferation within the recipient. This is accomplished through the introduction of adducts into the nucleic acids of CAR-T cell-derived effector cells following expansion in vitro to provide expanded and activated CAR-T cell-derived effector cells that retain immunologic function, including the expression of one ore more cytokines.

Abstract: Isolated mutant Mycobacterium tuberculosis bacteria comprising a deletion in the ESAT-6 gene cluster region 3 (esx-3 region) are provided, as well as compositions comprising such, methods of production thereof and methods of use thereof.

Abstract: The present invention relates generally to vaccine strains of Brachyspira hyodysenteriae. In particular, the present invention relates to isolated live vaccine strains of B. hyodysenteriae lacking one or more virulence factors. The present invention also relates to methods of identifying and preparing vaccine strains, as well as vaccine compositions against diarrhoeal diseases and methods and kits for diagnosing same.

Abstract: The present invention is directed to analgesic Clostridial neurotoxin derivatives comprising polypeptides having a long-lasting SNARE protein-selective endopeptidase activity. These derivatives selectively bind to and are internalized by non-neuronal cells secreting cytokines or sensory neurons in preference to motor neurons or autonomic neurons. The invention is also directed to nucleic acid constructs encoding such polypeptides, and methods of making such derivatives and nucleic acid constructs, and methods of treating pain, such as chronic pain, by administering such derivatives to a patient suffering from, or at risk of suffering from such pain.

Abstract: Shigella vaccine strains whose primary attenuating feature is deletion of the virG(icsA) gene and additional two or more deletions in setAB(shET1), senA(shET2), senB(shET2-2), stxAB, and msbB2 genes. Thus, the vaccine strain will have three or more deletions in the identified genes, will be safer, and will reduce or eliminate symptoms of fever and diarrhea in humans. The following specific vaccine strains have been constructed: WRSS3 (?senA, ?senB, ?virG, ?msbB2), WRSf2G15 (?virG, ?setAB, ?senA, ?senB, ?msbB2), and WRSd5 (?virG, ?stxAB, ?senA, ?senB, ?msbB2).

Abstract: Herpes Simplex Viruses are disclosed having single-chain antibodies (scFv) embedded in the viral envelope via fusion with glycoprotein D and with glycoprotein H and L.

Abstract: Gram negative bacterial virulence genes are identified, thereby allowing the identification of novel anti-bacterial agents that target these virulence genes and their products, and the provision of novel gram negative bacterial mutants useful in vaccines.

Abstract: This disclosure relates to modified Streptococcus pneumonia pneumolysm (PLY) proteins which lack hemolytic activity and can be used as immunogens in an immunogenic composition or vaccine against invasive pneumococcol diseases caused by S. pneumonia The modified pneumolysm proteins comprise amino acid substitutions at threonine 65, glycine 293 and cysteine 428 Nucleic acids, polypeptides encoded thereby, compositions containing the same, methods for using such nucleic acids, polypeptides and compositions are also provided.

Abstract: The present disclosure generally relates to genetic engineering of bacteria. More particularly, the present disclosure relates to genetic engineering of Gram-negative bacteria expressing different species of lipid A on their surface. In one embodiment, the present disclosure provides for an engineered strain of E. coli according to Table 1. In another embodiment, the present disclosure provides for a lipopolysaccharide purified from an engineered strain of E. coli according to Table 1.

Abstract: The present invention provides improved Pseudomonas Exotoxin A (PE) molecules with high cytotoxicity and reduced immunogenicity, compositions containing the improved (PE), and methods of use.

Abstract: The present invention encompasses a recombinant bacterium comprising a regulated rfaH nucleic acid, as well as a vaccine comprising said recombinant bacterium. Other embodiments of the present invention encompass a recombinant bacterium comprising a regulated rfaH nucleic acid and a regulated rfc nucleic acid, while additional embodiments encompass a recombinant bacterium comprising a regulated rfaH nucleic acid and at least one nucleic acid encoding at least one exogenous antigen.

Abstract: The invention provides live, attenuated enterohemorrhagic Escherichia coli (EHEC) bacteria in which the Shiga toxin coding sequences are deleted to abolish Shiga toxin production and one or more of the nucleotide sequences for the bacterial adhesin protein intimin, the locus of enterocyte effacement encoded regulator, and the translocated intimin receptor are mutated to inactivate the activity of the encoded protein(s). This live, attenuated E. coli bacteria is used in a vaccine for reducing or inhibiting carriage and shedding of EHEC in cattle.

Abstract: Embodiments of the invention include methods and compositions useful in a vaccination strategy capable of neutralizing HIa to provide immunoprotection against S. aureus pneumonia. In certain aspects the invention includes a HIa with reduced toxicity, represented by a recombinant mutant form of HIa (HlaH35L) in which histidine 35 is converted to leucine, which can be used to abrogate the productive assembly of the toxin and protect a subject from staphylococcal pneumonia.

Abstract: Methods and compositions for the treatment of Brucella induced diseases and disorders are disclosed herein. In preferred embodiments, the invention relates to vaccines. In additional embodiments, the invention relates to formulations capable of releasing said vaccines at a controlled rate of release in vivo. In further embodiments, the invention relates to modified strains of the bacteria Brucella melitensis and Brucella abortus. In still further embodiments, the invention relates to compositions that do not induce clinical symptoms or splenomegaly in a subject receiving said compositions.

Abstract: The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve a non-toxigenic Protein A (SpA) variant.

Abstract: The present invention relates to vaccines for control of Borrelia infections in animal and human populations. In particular, the present invention provides compositions and methods comprising recombinant bacteria engineered to express one or more Borrelia burgdorferi antigens for use as Lyme disease vaccines. In some embodiments, the recombinant bacteria are freeze-dried.

Abstract: The invention provides liquid rotavirus formulations that are suitable for oral administration to human infants. In particular the invention provides pharmaceutical compositions and vaccines, comprising a rotavirus antigen, a sugar and a carboxylate wherein said formulation has a pH of between pH 5.0 and pH 8.0 and comprises no phosphate or less than 5 mM phosphate. The invention also provides methods of preparing said rotavirus formulations and use thereof in the prevention or treatment of rotavirus associated diseases in humans.

Abstract: The present invention provides a method for generating negative-strand, segmented RNA viruses using linear expression constructs in the presence of helper virus.

Abstract: The invention relates to Gram-negative bacteria carrying an inactivated gene encoding a glycosyltransferase involved in the synthesis of the core of the LPS of said Gram-negative bacteria, wherein said inactivated gene results in the synthesis of a LPS having a modified core. These strains have an attenuated virulence but induce a humoral immunity sufficient for ensuring vaccination of the host.

Abstract: The disclosure features vaccine adjuvants comprising prokaryotic mRNA, and methods of vaccination using the adjuvants. More specifically, the disclosure provides a vaccine composition comprising a nonviable immunogen (e.g., heat-killed bacterium), a tumor antigen, or an immunogenic peptide of microbial or mammalian origin, and an adjuvant, wherein adjuvant comprises prokaryotic mRNA (e.g., bacterial mRNA), as well as the methods of using the vaccine compositions. Further disclosed are the structural features of the prokaryotic mRNA used as the adjuvants.

Abstract: This disclosure relates to modified Streptococcus pneumonia pneumolysm (PLY) proteins which lack hemolytic activity and can be used as immunogens in an immunogenic composition or vaccine against invasive pneumococcol diseases caused by S. pneumonia. The modified pneumolysm proteins comprise ammo acid substitutions at threonine 65, glycine 293 and cysteine 428 Nucleic acids, polypeptides encoded thereby, compositions containing the same, methods for using such nucleic acids, polypeptides and compositions are also provided.

Abstract: The invention relates to Pasteurella multocida mutants capable of providing heterologous protection against infection caused by virulent P. multocida . Said mutants are defective in fur ompH and fur ompH galE genes. The invention relates to Pasteurella multocida bacteria vaccine compositions containing fur ompH double mutants and fur ompH galE triple mutants obtained from P. multocida , or an extract of iron-regulated outer-membrane proteins (IROMPs) obtained from said mutants, and to an excipient and/or pharmaceutically acceptable adjuvants.

Abstract: The present invention relates a combination for use in the treatment and/or prevention of mastitis containing i) an agonistic anti-CD40 monoclonal antibody or a CD40 ligand or a vector coding for the anti-CD40 antibody or a vector coding for the CD40L; and ii) inactivated or attenuated bacteria selected from the group consisting of Staphylococcus, Streptococcus, Listeria or Escherichia.

Abstract: This invention relates to compositions for delivering one or more active ingredients, and more particularly to compositions, e.g. beads, comprising a matrix material which matrix material comprises a microorganism. In particular, the invention relates to compositions comprising a microorganism selected from live, killed, attenuated and inactivated microorganisms. The matrix material may also comprise a surfactant and may further comprise an adjuvant. The invention further relates to the manufacture and use of such compositions, and to other subject matter.

Abstract: The present invention relates to a mutated Francisella bacterium, wherein the ggt gene is silenced or deleted; pharmaceutical compositions comprising the same, in particular, vaccine compositions, and use of the bacterium and compositions for treatment and/or prophylaxis, and in particular, the treatment or prophylaxis of tularemia.

Abstract: A high throughput bioluminescence mutant screening procedure is disclosed. This procedure utilizes robotics, and bacterial luciferase to allow real-time monitoring of mutant viability. The procedure was used to decelop a live attenuated vaccine for a catfish against E. ictaluri, which is further claimed herein. Additionally, genes from other bacterial species are disclosed which may also be used to create vaccines.

Abstract: The present invention relates to avirulent Salmonella Gallinarum variants by inactivating virulence gene clusters of Salmonella Gallinarum (SG), a main pathogen of avian salmonellosis, and various uses thereof notably in the production of Salmonella-specific lytic bacteriophages, pharmaceutical compositions and feed additives.

Abstract: The preset invention relates to an oral vaccine with an enhanced protective efficacy for aquatic animals comprising an antigen, which is expressed in Listonella sp., such as L. anguillarum, as an expression host transformed with an expression vector comprising the nucleic acid encoding the antigen, such as a viral subunit.

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

Abstract: The present invention relates to avirulent Salmonella gallinarum variants by inactivating virulence gene clusters of Salmonella gallinarum (SG), a main pathogen of avian salmonellosis, and various uses thereof notably in the production of Salmonella-specific lytic bacteriophages, pharmaceutical compositions and feed additives.

Abstract: The present invention is drawn to a live, attenuated S. Paratyphi A strain, a live, attenuated S. Paratyphi A strain comprising a stabilized plasmid expression system, and methods of using these strains.

Abstract: The present invention relates to an attenuated Salmonella typhi having mutation in chromosomal gene loci, its use as a potent vaccine candidate to combat the Salmonella infection.

Abstract: The present invention provides for a method of reducing the reactogenicity of live attentuated bacterial vaccines by deleting at least a portion (e.g., the TLR-5 stimulating domain of a flagellin protein) of at least one of the bacterial genes that encodes a flagellin from the bacterium genome. These vaccines are directed against enteric or non-enteric flagellin-producing bacteria. A particular embodiment provides for a live attenuated cholera vaccine having reduced reactogenicity.

Abstract: The present invention relates to avirulent Salmonella Gallinarum variants by inactivating virulence gene clusters of Salmonella Gallinarum (SG), a main pathogen of avian salmonellosis, and various uses thereof notably in the production of Salmonella-specific lytic bacteriophages, pharmaceutical compositions and feed additives.

Abstract: Oral immunogenic compositions imparting dual protection against enterotoxigenic labile toxin (LT)-expressing Escherichia coli (ETEC) and Vibrio cholerae based on the delivery of recombinant cholera toxin B antigen by attenuated, live bacterial vectors derived from Vibrio cholerae are disclosed. The compositions exhibit dual immunogenicity and retain the ability to colonize gastrointestinal mucosa-associated lymphoid tissues.

Abstract: The present invention provides Listeria that are attenuated for entry into non-phagocytic cells as well as a variety of methods of inducing immune responses involving administering compositions comprising the attenuated Listeria. Some of the attenuated Listeria are mutant Listeria that comprise at least one mutation in a gene encoding an invasin, such as an internalin. Some of the attenuated Listeria are further attenuated for cell-to-cell spread. Pharmaceutical compositions and vaccines useful in the methods of the invention are further provided. Methods of making and improving vaccines are also provided.

Abstract: The invention provides compositions of inactivated influenza virus that can be used as vaccines and immunological compositions useful for inhibiting, preventing and treating influenza.

Abstract: This invention provides liquid rotavirus formulations that are suitable for oral administration to human infants. In particular, the invention provides pharmaceutical compositions and vaccines, comprising a rotavirus antigen, a sugar and a carboxylate, wherein said formulation has a pH of between pH 5.0 and pH 8.0 and comprises no phosphate or less than 5 mM phosphate. The invention also provides methods of preparing said rotavirus formulations and use thereof in the prevention or treatment or rotavirus associated diseases in humans.

Abstract: The present invention relates to a mutated Francisella bacterium, wherein the ggt gene is silenced or deleted; pharmaceutical compositions comprising the same, in particular, vaccine compositions, and use of the bacterium and compositions for treatment and/or prophylaxis, and in particular, the treatment or prophylaxis of tularemia.

Abstract: The disclosure relates generally to an antigenic composition useful for immunization against tularemia. The disclosure is a method for producing a vaccine for preventing tularemia in humans and animals, a new vaccine against tularemia in humans and animals, and a new approach to producing vaccines against tularemia.

Abstract: The present invention provides MSCRAMM® proteins from S. aureus which are putative highly-expressed antigens from methicillin-resistant S. aureus, including communit-associated MRSA (CA-MRSA), and these antigens can thus be utilized in methods of generating antibodies capable of binding these antigens which can be useful in methods of treating or preventing infection from MRSA. The present invention is directed to these proteins, antibodies capable of binding these proteins, methods of generating said antibodies, nucleic acids coding for said proteins, and pharmaceutical compositions or vaccines which include the proteins or antibodies of the present invention in combination with a pharmaceutically acceptable vehicle, carrier or excipient.

Abstract: Methods for treating proliferative disorders, by administering reovirus to a Ras-mediated proliferative disorder, are disclosed. The reovirus is administered so that it ultimately directly contacts ras-mediated proliferating cells. Proliferative disorders include but are not limited to neoplasms. Human reovirus, non-human mammalian reovirus, and/or avian reovirus can be used. If the reovirus is human reovirus, serotype 1 (e.g., strain Lang), serotype 2 (e.g., strain Jones), serotype 3 (e.g., strain Dearing or strain Abney), as well as other serotypes or strains of reovirus can be used. Combinations of more than one type and/or strain of reovirus can be used, as can reovirus from different species of animal. Either solid neoplasms or hematopoietic neoplasms can be treated.

Abstract: Methods for prophylaxis or treatment of sepsis in a subject are provided comprising administering to the subject a therapeutically effective dose of multiple deletion strain bacteria.

Abstract: The invention provides recombinant Listeria that constitutively express Prf A and comprise polynucleotides that encode polypeptides such as tumor or infectious agent antigens, operably linked to a PrfA responsive regulatory agent. Methods of using the Listeria, and compositions thereof, to induce or enhance an immune response and/or in the treatment of disease are provided. Methods of producing the bacteria are also provided.

Abstract: Method for producing multiple modifications in the chromosome of Gram-negative bacteria and Salmonella strains which are deficient in c-di-GMP synthesis obtained by said method. The method can be used to make multiple modifications in the genome of Gram-negative bacteria, simply and efficiently, using the plasmids of the invention, which comprise a marker gene under the control of a constitutive promoter, a replication origin specific for Gram-negative bacteria, a gene which encodes a heat-sensitive protein essential for initiating replication of the plasmid, making the replication origin heat-sensitive, and a counter-selection gene.

Abstract: A method for identifying a microorganism having a reduced adaptation to a particular environment comprising the steps of: (1) providing a plurality of microorganisms each of which is independently mutated by the insertional inactivation of a gene with a nucleic acid comprising a unique marker sequence so that each mutant contains a different marker sequence, or clones of the said microorganism; (2) providing individually a stored sample of each mutant produced by step (1) and providing individually stored nucleic acid comprising the unique marker sequence from each individual mutant; (3) introducing a plurality of mutants produced by step (1) into the said particular environment and allowing those microorganisms which are able to do so to grow in the said environment; (4) retrieving microorganisms from the said environment or a selected part thereof and isolating the nucleic acid from the retrieved microorganisms; (5) comparing any marker sequences in the nucleic acid isolated in step (4) to the unique mar