Abstract: The present invention provides methods for treating an animal having a high somatic cell count. The methods include administering compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter.

Abstract: The present invention provides compositions including at least two siderophore receptor polypeptides and at least two porins from a gram negative microbe, and preferably, lipopolysaccharide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of makino and methods of using such compositions.

Abstract: The present invention provides methods for treating an animal for low milk production. The methods include administering compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter.

Abstract: Disclosed herein are antigens that stimulate protective antibodies against enterotoxigenic Escherichia coli. Also disclosed herein are proteins encoded by cssA and cssB genes as well as constructs containing the genes and methods of using thereof.

Abstract: A non-toxic mucosal adjuvant is provided which may be admixed with further antigens to provide a vaccine administrable to mucosal surfaces in organisms including man. Preferably, the non-toxic mucosal adjuvant is a detoxified mutant of a bacterial ADP-ribosylating toxin, optionally comprising one or more amino acid additions, deletions or substitutions.

Abstract: The present invention provides a novel composition which is a hybrid heat labile enterotoxin comprising the A-subunit of the heat labile toxin of Escherichia coli (LT-A) and the B-subunit of the cholera enterotoxin of Vibrio cholerae (CT-B). The hybrid toxin is designated LT-A/CT-B. The LT-A subunit, the CT-B subunit, or both subunits of the hybrid toxin may be mutant subunits, e.g., differing from wild-type subunits by amino acid substitutions, deletions or additions. Also provided are methods of using the novel LT-A/CT-B comprising compositions of the invention as adjuvants for vaccines, methods of making the LT-A/CT-B hybrid holotoxin, and kits.

Abstract: The present invention provides parenteral adjuvants comprising detoxified mutants of bacterial ADP-ribosylating toxins, particularly those from pertussis (PT), cholera (CT), and heat-labile E. coli (LT).

Abstract: The present invention discloses fusion proteins of the immunodominant antigens ESAT-6 and Ag85B from Mycobacterium tuberculosis or homologues thereof, and a tuberculosis vaccine based on the fusion proteins, which vaccine induces efficient immunological memory.

Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.

Abstract: A vaccine, effective in inducing the production of antibodies with which to immunize a second subject passively against infection by Gram-negative bacteria and LPS-mediated pathology, comprises a non-covalent polyvalent complex formed between purified, detoxified LPS derived from E. coli and purified outer membrane protein derived from N. meningitidis. The same vaccine will also actively immunize a host subject against Gram-negative bacterial infections and LPS-mediated pathology. Meningococcal infections are included among those Gram-negative bacterial infections protected against by the vaccine.

Abstract: A vaccine, effective in inducing the production of antibodies with which to immunize a second subject passively against infection by Gram-negative bacteria and LPS-mediated pathology, comprises a non-covalent polyvalent complex formed between purified, detoxified LPS derived from E. coli and purified outer membrane protein derived from N. meningitidis. The same vaccine will also actively immunize a host subject against Gram-negative bacterial infections and LPS-mediated pathology. Meningococcal infections are included among those Gram-negative bacterial infections protected against by the vaccine.

Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.

Abstract: The present invention describes the isolation and purification of histidine-tagged functional portions of intimin (his-tagged intimin or his-intimin), a protein associated with the ability of certain strains of pathogenic bacteria to adhere to epithelial cells. The invention further describes the use of intimin as an antigen to promote a protective immune response. In addition, the invention describes the combination of intimin with one or more other antigens and administration of the combination to promote a protective immune response against intimin and the one or more antigens. One aspect of the invention is the administration of intimin to target specific epithelial cells to promote a protective immune response to intimin proteins. Additional aspects of the invention include the use of intimin or intimin combined with one or more antigens and administration of the combination to target gastrointestinal mucosa and stimulate an immune response.

Abstract: The invention features incapacitated whole cell bacterial immunogenic compositions produced by infecting a bacterium with Lys minus bacteriophage, which are deficient in the lysin protein. Lys minus bacteriophage retain activity in infection of its appropriate bacterial host, destruction of the bacterial genome, and replication, which are sufficient to inhibit bacterial growth and replication. The resulting, Lys minus-infected bacterium is provided in a state of bacteriostasis, and is not capable of replicating further (e.g., is “incapacitated”). The incapacitated bacterium can then be used as to elicit an immune response for prophylactic and/or therapeutic purposes. The invention thus also features incapacitated bacteria formulated appropriately for use in immunogenic compositions for eliciting an immune response, e.g., for production of antibodies in a non-human host or in a whole cell bacterial vaccine.

Abstract: The invention relates to a vaccine comprising a bacterium attenuated by a non-reverting mutation in a gene encoding a protein which promotes folding of extracytoplasmic proteins. Such mutations were initially identified as being useful in vaccines from a bank of randomly inserted, transposon mutants in which attenuation was determined as a reduction in virulence of the organism in the mouse model of infection. Site directed mutation of the gene results in a strain which shows at least 4 logs of attenuation when delivered both orally and intravenously. Animals vaccinated with such a strain are protected against subsequent challenge with the parent wild type strain. Finally, heterologous antigens such as the non-toxic and protective, binding domain from tetanus toxin, fragment C, can be delivered via the mucosal immune system using such strains of bacteria. This results in the induction of a fully protective immune response to subsequent challenge with native tetanus toxin.

Abstract: Compositions comprising products of the csa operon, an isolated nucleic acid encoding the csa operon or functional fragments thereof, purified polypeptide products of the csa operon or functional fragments thereof, methods of eliciting an immune response to these products, and methods of producing products of the csa operon are disclosed herein.

Abstract: The invention encompasses methods of maintaining desired recombinant genes in a genetic population of cells expressing the desired gene. The methods utilize microbial cells that have an inactivating mutation in a native essential gene encoding an enzyme which catalyzes a step in the biosynthesis of diaminopimelic acid (DAP). The cells also have an extrachromosomal vector that includes the desired gene and which is capable of homologous recombination with a chromosome of the microorganism. The vector also has a recombinant complementing gene encoding a functional replacement of the native essential gene. The cells of the invention are particularly useful for components of vaccines, including DNA vaccines.

Abstract: The present invention relates to a vaccine containing at least one particulate immunogen and an adjuvanting amount of B subunits of heat-labile enterotoxin characteristic of E. Coli. More in particular, this invention relates to vaccines wherein the adjuvanting LTB is free from contaminating A subunits or holotoxin. To this end, preferably, use is made of LTB prepared by recombinant DNA techniques. The particulate immunogens can relate to or can be derived from e.g. viruses, bacteria or fungi. This vaccine is particularly suitable for the induction of a protective response against said particulate immunogen upon mucosal (e.g. intra-nasal) administration. It was found that such administration results in both systemic and mucosal protection against the pathogen to which the particulate immunogen relates.

Abstract: A vaccine delivered by transcutaneous immunization provides an effective treatment against infections by pathogens such as, for example, enterotoxigenic Escherichia coli (ETEC) and/or for symptoms of diarrheal disease caused thereby. For example, one, two, three, four, five or more antigens derived from ETEC and capable of inducing an antigen-specific immune response (e.g., toxins, colonization or virulence factors) and one or more optional adjuvant (e.g., whole bacterial ADP-ribosylating exotoxins, B subunits or toxoids thereof, detoxified mutants and derivatives thereof) are used to manufacture vaccines or to induce systemic and/or mucosal immunity.

Abstract: Compositions and methods for making complex carbohydrates in a bacterial production cell are disclosed. The complex carbohydrates that can be made include oligosaccharides and polysaccharides of bacterial or mammalian origin.

Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. Also provided are methods for vaccination of mammalian species, especially human patients, with variants of the E. coli FimH protein, said variants being derived from different strains of E. coli, and to production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A plasmid-based method of producing polypeptides, especially fused polypeptides, such as the complex of a bacterial chaperone and a bacterial adhesin, is also disclosed.

Abstract: The present invention pertains generally to Neisseria meningitidis serogroup B glycoconjugates. More particularly, the invention pertains to glycoconjugates formed from a Neisseria meningitidis serogroup B capsular oligosaccharide derivative (MenB OS derivative) in which sialic acid residue N-acetyl groups are replaced with N-acyl groups. The invention also pertains to vaccine formulations containing the glycoconjugates, methods of making the vaccine formulations, and methods of using the vaccine formulations to treat or prevent Neisseria meningitidis serogroup B or E. coli K1 disease in a mammalian subject.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: The present invention relates to live attenuated gram-negative vaccine carrier strains which are useful for expression and delivery of heterologous O-antigens (O-PS) from gram-negative pathogens. Said strains are deficient in the expression of homologous O-PS due to a defined genetic modification, preferably a deletion, and, thus, capable of efficiently expressing a desired heterologous O-PS in such a way that it is covalently coupled either to homologous or heterologous LPS core lipid A. The present invention furthermore relates to live vaccine carrier strains containing a heterologous gene or a set of heterologous genes encoding O-PS. Preferably, said strains additionally contain genes necessary for the synthesis of complete smooth heterologous LPS. The present invention also relates to live vaccines comprising said strains, preferably for immunization against gram-negative enteric pathogens.

Abstract: The invention relates to chemically-modified group B polysaccharides of Neisseria meningitidis. The invention also provides vaccines in which the respective modified polysaccharides are conjugated to a protein carrier, and the like. More specifically, the present invention provides novel group B meningococcal unsaturated N-acyl derivative polysaccharides, novel conjugates of the group B meningococcal unsaturated N-acyl derivative polysaccharides, pharmaceutical compositions comprising conjugate molecules of group B meningococcal unsaturated N-acyl derivative polysaccharide fragments covalently bound to proteins, and the use of these compositions as vaccines.

Abstract: Disclosed is a method of producing a vaccine composition against enteric infection caused by enterotoxigenic E. coli bacteria in humans. E. coli strains selected from different known strains each having the ability of expressing a certain type of colonization factor antigens are grown in a liquid culture medium. Finally formalin-killed E. coli strain having substantially preserved antigenic and hemagglutinating properties of said certain type of colonization factor antigens, is mixed with a pharmaceutically acceptable excipient and/or diluent. Further disclosed is a method of preventing an enteric infection caused by enterotoxigenic E. coli bacteria in humans, whereby a vaccine composition comprising inactivated E. coli strain is administered to a human being for the prevention of said infection.

Abstract: This invention features an oral vaccine that includes a multiple-cell organism for use as food for an aquatic animal to be vaccinated, and a single-cell organism fed to, and as a result, bioencapsulated by, the multiple-cell organism. The single-cell organism has been transformed to express a recombinant antigen that induces an immune response in the aquatic animal and thereby vaccinates the aquatic animal (e.g., a fish or a shrimp).

Abstract: The present invention provides compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such compositions.

Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.

Abstract: Compositions and methods for stimulating an immune response against a secreted enterohemorragic Escherichia coli (EHEC) antigen are disclosed. The compositions comprise EHEC cell culture supernatants.

Abstract: Fimbriae adhesins have a molecular weight of 2×105 and 2×107 Da, and are comprised of 90-95% protein and 1-3% sugar. Type 1 fimbriae include five different protein fractions of 14-20 kDa, most of which are associated with carbohydrates. Type P fimbriae also include five different protein fractions of 14-20 kDa, and one of the majority proteins is associated with carbohydrates. The process of the invention comprises: culturing E. coli strains CECT 4484 and CECT 4485; collecting the sediment by centrifugation and resuspending it in physiological saline followed by homogenization; centrifuging the homogenate and collecting the supernatant; precipitating the supernatant with saline, reconstituting the precipitate and dialyzing the solution; treating the dialyzate with sodium deoxycholate and, subjecting the product to two successive chromatographies with Sephacryl S-200 and Sepharose 4B. The product is used for treatment and prevention of infections of the urinary tract caused by fimbriated E. coli.

Abstract: The invention relates to antigenic preparations and vaccines directed against the porcine multisystemic wasting syndrome (PMWS), comprising at least one porcine circovirus antigen, preferably type II, and at least one porcine parvovirus antigen.

Abstract: Methods and compositions are provided herein for the se of a novel mutant form of E. coli heat-labile enterotoxin which has lost its toxicity but has retained its immunologic activity. This enterotoxin is used in combination with an unrelated antigen to achieve an increased immune response to said antigen when administered as part of an oral vaccine preparation.

Abstract: The invention provides a vaccine for immunizing poultry and other animals against infection by a gram-negative bacteria, and a method of immunizing an animal using the vaccine. The vaccine may contain purified siderophore receptor proteins derived from a single strain or species of gram-negative bacteria or other organism, which are cross-reactive with siderophores produced by two or more strains, species or genera of gram-negative bacteria. The invention further provides a process for isolating and purifying the siderophore receptor proteins, and for preparing a vaccine containing the proteins. Also provided is a method for diagnosing gram-negative sepsis.

Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.

Abstract: The present invention is directed towards compositions containing pathogenic bacteria (e.g. Haemophilus, E. Coli, and/or Salmonella) having non-reverting genetic mutations which alter activity of DNA adenine methylase (Dam) and methods using these compositions to elicit an immune response to produce highly specific antibodies. The invention also provides methods for preparing vaccines as well as screening methods to identify agents which may have anti-bacterial activity.

Abstract: The oral antigens and adjuvants of the present invention are produced in transgenic plants and then administered through the consumption of the transgenic plant. DNA sequences both natural and synthetic encoding for the expression of immunogenic agents which are capable of causing an immune response in animals when fed in edible plants, plant tissues, or derived plant materials are constructed, and plants transformed for stable or transient expression in plant cells. The present invention provides the first known functional method for immunizing animals via transgenic plants, where the plants express bacterial antigens that act as both immunogen and adjuvants when the transgenic plant material expressing the antigens is fed to animals.

Abstract: The present inventors have found that certain preparations containing LPS and/or lipid A variants, derivatives, and/or analogs demonstrate non-pyrogenic properties and exhibit anti-viral activities. In particular, non-pyrogenic preparations of LPS, lipid A, LPS antagonists and lipid A antagonists, and derivatives thereof induce &bgr; chemokine secretion, such as MIP-1&bgr;, but not proinflammatory cytokines, such as TNF&agr;, IL-1&bgr; and IL-6. Non-pyrogenic preparations of the invention have been demonstrated by the Applicant to suppress HIV replication in human peripheral blood monocytes, as described by way of example herein. The present invention provides preparations of LPS or lipid A variants, analogs and derivatives of decreased or absent pyrogenicity which can be used as therapeutics for the treatment or prevention of immunodeficiency virus infection and its consequences.

Abstract: “Black holes” in the genomes of bacterial pathogens represent deletions of “anti-virulence” genes, i.e. genes that are detrimental to a pathogenic lifestyle. Identification of the missing genetic loci in the “black hole” identifies genes that are incompatible with the bacteria's pathogenicity. These genes, their gene products, and compounds generated by the enzymatic action of these gene products represent potential new compounds that are inhibitory to the bacterial pathogen and thus useful as pharmaceuticals. The utility of this concept is demonstrated in the missing gene for lysine decarboxylase, and the resulting inhibitory activity of cadaverine (the diaminoalkyl reaction product of lysine decarboxylase) on the Shigella enterotoxins. Diaminoalkyl compounds are therefore potent inhibitors of E. coli and Shigella spp. enterotoxins. Lysine decarboxylase generated from the gene cadA results in attenuation of the enterotoxic effects.

Abstract: A vaccine for the immunization of domestic fowl, such as turkeys and chickens, against E. coli infections (Colibacillosis) is disclosed which contains an effective amount of a live temperature sensitive mutant of E. coli dispersed in a physiologically acceptable, non-toxic liquid vehicle. The E. coli mutant disclosed exhibits growth at 32° C. but not at 41° C. and has a reversion frequency of less than about 1×10−8.

Abstract: The invention pertains to adjuvant and vaccine compositions of monophosphoryl lipid A, sugar and optionally an amine based surfactant, which when frozen and thawed or lyophilized and reconstituted reform a colloidal suspension having a light transmission of greater than or equal to 88% as measured spectrophotometrically.

Abstract: The present disclosure provides methods and compositions for inducing an immune response to an antigen, especially in an immunogenic composition comprising sialic acid where the antigen comprises sialic acid and wherein the immunogenic composition further comprises a sialic acid binding component, e.g., an inactivated or attenuated paramyxovirus or orthomyxovirus such as an influenza virus comprising a sialic acid binding component, e.g., a neuraminidase. The compositions comprising sialic acid and a sialic acid binding component effectively induce a humoral immune response even in a human or animal which is deficient in CD4+ T cells, due to a disease such as ARC or AIDS, and there is also an immunoglobulin class switching even in the absence of CD4+ T cells.

Abstract: Bacterial antigen preparations for use as live or killed immunogens and vaccines can be produced by culture of bacteria such as Neisseria in medium comprising norepinephrine or other catechol-group-containing growth inducer of bacterial growth, harvesting and pharmaceutical formulation. The antigen preparations can comprise bacterial protein(s) inducible by norepinephrine.

Abstract: The present invention provides nucleic acid sequences coding for two ryegrass pollen allergen Lol p Ib family members, purified Lol p Ib.1 and Lol p Ib.2 proteins and fragments thereof, methods of producing recombinant Lol p Ib.1 or Lol p Ib.2 or at least one fragment thereof or derivative or homologue thereof, and methods of using the nucleic acid sequences, proteins and peptides of the invention.

Abstract: Liposome encapsulated antibiotic therapy has limited application against infectious organisms, which can sequester in non-phagocytic cells. Virulence factors of these infectious organisms, for example bacterial components, when used in the formulation of liposomes can enhance the effectiveness of liposomes as delivery systems in the treatment of disease. In this manner, multi-functional liposomes can be developed to treat target diseases. In addition to serving as antibiotic delivery systems, such liposomes also have an immunization effect. Thus, the liposomes can be used for both the prevention and treatment of diseases.

Abstract: The invention relates to antigenic preparations and vaccines directed against the porcine multisystemic wasting syndrome (PMWS), comprising at least one porcine circovirus antigen, preferably type II, and at least one porcine parvovirus antigen.