Abstract: A method for modifying a wild strain of an entero-invasive Shigella to produce a modified strain of Shigella that can be used for making a vaccine against the wild strain of Shigella. The genome of the wild strain of Shigella is transformed so that it cannot substantially invade cells of a human host and cannot spread substantially within infected cells and from infected to uninfected cells of the host and cannot produce toxins which will kill substantial numbers of the host's infected, as well as uninfected, cells. A first gene of the wild strain of Shigella, coding for a protein necessary for the Shigella to invade cells of the host, and a second gene, coding for a protein necessary for the Shigella to spread within infected cells and between the infected and uninfected cells of the host, are mutagenized.

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 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 invention relates to peptides comprising an amino acid sequence homologous to the amino sequence of a fragment of a pyrogenic exotoxin, and functional derivatives of said peptides, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins. Preferred peptides comprise an amino acid sequence homologous to the amino sequence of a fragment of Staphylococcal aureus enterotoxin B (SEB). The invention also relates to broad spectrum pharmaceutical compositions for the treatment, protection against or short term prophylaxis of toxin-mediated activation of T cells, comprising as active ingredient at least one peptide according to the invention or derivative thereof, and to broad spectrum vaccines for conferring long term immunity against toxic shock induced by at least one pyrogenic exotoxin are provided. The vaccines comprising as active ingredient at least one peptide according to the invention, or derivative thereof.

Abstract: Antibodies, polypeptides, and polynucleotides are provided for the detection, prevention, amelioration and treatment of diseases caused by Actinobacillus actinomycetemcomitans.

Abstract: The present invention relates to live attenuated Salmonella strains comprising a first attenuating mutation, that are not capable of making functional RecA. The invention also relates to these bacteria for use in vaccines. Furthermore, the invention relates to vaccines based upon these bacteria, to the use of such bacteria in the manufacture of vaccines and to methods for the preparation of such vaccines.

Abstract: The invention concerns an acellular immunogenic or vaccine composition for producing antibodies against Bacillus anthracis comprising a protective antigen (PA) and killed and optionally purified spores, obtained from mutating strains of Bacillus anthracis and their uses.

Abstract: A negatively-charged Staphylococcus antigen contains amino acids and a N-acetylated hexosamine as a major carbohydrate component. The antigen is common to many coagulase-negative strains of Staphylococcus, including S. epidermidis, S. haemolyticus, and S. hominis. Staphylococcus strains that carry the antigen include many clinically significant strains of Staphylococcus. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing Staphylococcus infection. Vaccines of the antigen and of whole cells that carry the antigen also are disclosed.

Abstract: The present invention is directed to mutant Salmonella sp. having a genetically modified msbB gene in which the mutant Salmonella is capable of targeting solid tumors. The present invention further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.

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: The present invention is directed to mutant Salmonella sp. having a genetically modified msbB gene in which the mutant Salmonella is capable of targeting solid tumors. The invention is also directed to Salmonella sp. containing a genetically modified msbB gene as well as an genetic modification in a biosynthetic pathway gene such as the purI gene. The present invention further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.

Abstract: The production of a purified extracellular bacterial signal called autoinducer-2 is regulated by changes in environmental conditions associated with a shift from a free-living existence to a colonizing or pathogenic existence in a host organism. Autoinducer-2 stimulates LuxQ luminescence genes, and is believed also to stimulate a variety of pathogenesis related genes in the bacterial species that produce it. A new class of bacterial genes is involved in the biosynthesis of autoinducer-2.

Abstract: The present invention discloses a DNA fragment that can direct the insertion of heterologous DNA into a specific site (tRNAAla gene) of Mycobacterium spp. genome. This DNA fragment includes the attachment site region (attP) and the integrase gene of the mycobacteriophage Ms6. Heterologous DNA linked to this DNA fragment can be carried into the mycobacterial genome through a site-specific integration mechanism. A new DNA integration process is disclosed that consists in providing the integrase gene on a suicide vector, that transiently produces the integrase required for the insertion of the gene or genes linked to the Ms6 attP region contained in a separated plasmid vector. This process allows the construction of highly stable recombinant mycobacteria which may be used as vaccines and/or therapeutic vehicles.

Abstract: The invention concerns a reagent for diagnosing an infection caused by a virus, characterized in that it comprises essentially a mixture consisting of (1) an immunodominant fragment of a protein of said virus comprising not more than 60 aminoacids, preferably between 20 and 30 aminoacids and (2) a mixture (called mixotope) of convergent combining peptides, derived from said immunodominant fragment, which peptides are obtained by total or partial artificial degeneration of said immunodominant fragment by systematic or partial replacement of each aminoacid by another according to an appropriate substitution matrix. The invention concerns a reagent for detecting and monitoring infections caused by the Epstein-Barr virus of EBV, which is, in particular, the causal agent of infectious mononucleose and its applications for detecting an EBV infection at any stage of the infection (primo-infection, healthy carriers and induced tumors).

Abstract: Methylation of DNA can be a critical step in the introduction of DNA into P. haemolytica. A methyltransferase has been isolated and molecularly cloned for this purpose. Use of the methyltransferase has allowed construction of defined, attenuated mutants for use as vaccines to protect cattle.

Abstract: The present invention provides a isolated bacteriophage useful as a tool for studying biological, biochemical, physiological and genetic properties of actinomycetes and other organisms which comprises a novel strain of Saccharomonospora having certain specified characteristics. The invention also relates to a process for the isolation of the said bacteriophage and/or DNA phage and to a novel universal growth medium which is particularly useful in the said process. Another embodiment of the process relates to a clonong vector which comprises a plasmid or bacteriophage comprising the phage DNA of the invention.

Abstract: The present invention relates to live attenuated RTX-toxin producing bacteria of the family Pasteurellaceae, of which the attenuation is due to the fact that they produce RTX toxin in a non-activated form. The invention also relates to vaccines for the protection of mammals against infection with RTX-toxin producing bacteria of the family Pasteurellaceae, and to methods for the preparation of said live attenuated bacteria and vaccines.

Abstract: The invention related to novel Borrelia, and OspA antigens derived therefrom. These antigens show little homology with know OspA's and are therefore useful as vaccine and diagnostic reagents. Multicomponent vaccines based on OspA's from different Borrelia groups are also disclosed.

Abstract: Methods for eliciting or enhancing immune responses to antigens, including tumor antigens, and/or DNA vaccines are provided. The methods employ polypeptides or nucleic acid compositions that contain at least a biologically active portion of a Leishmania braziliensis or Leishmania major homologue of the eukaryotic initiation factor 4A, or a variant thereof. Such polypeptides and compositions are useful for enhancing or eliciting a patient's cellular and/or humoral immune response, for instance within methods for treating tumors.

Abstract: The present invention relates to nanoparticles comprised of a carrier, particularly polymerized lipids, and ligands displayed on the carrier, wherein the ligands form a polyvalent binding unit that is effective to produce a specific interaction between the nanoparticle and receptors on a target, particularly under physiologically relevant shear conditions.

Abstract: The present invention relates to a method of protecting pigs against disease caused by infection by heterologous serotypes of Salmonella including but not limited to S. typhimurium comprising administering to the pigs a modified live vaccine incorporating S. cholerasuis.

Abstract: Bovine respiratory disease (BRD) complex, shipping fever, or pneumomic pasteurellosis, is a multifactorial disease whereby a combination of viral infection, adverse environment and poor immune status may combine to predispose animals to bacterial infections. The exotoxin, or leukotoxin (Lkt), may contribute to pathogenesis by impairing the primary lung defenses and subsequent immune responses or by causing inflammations as a result of leukocyte lysis. The present invention provides a modified microorganism which produces an Lkt toxin, wherein said Lkt toxin is partially or fully inactivated. In a further embodiment of the present invention, there is provided a modified microorganism wherein an Lkt toxin operon including an Lkt structural gene and/or a post transational activator of the organism is partially or fully inactivated. The present applicants have found that a precursor of Lkt toxin has reduced toxic activity.

Abstract: The present invention provides a recombinant M. tuberculosis mycobacterium that is auxotrophic for leucine. The present invention also provides a vaccine comprising a recombinant M. tuberculosis mycobacterium that is auxotrophic for leucine, as well as a method for treating or preventing tuberculosis in a subject comprising administering to the subject a recombinant M. tuberculosis mycobacterium that is auxotrophic for leucine in an amount effective to treat or prevent tuberculosis in the subject.

Abstract: There is provided an assay suitable for the typing of bacterial strains. In the assay a predetermined amount of phage is combined with a bacterial isolate of unknown strain, the mixture being located in a suitable container. The mixture of phage and bacteria is conveniently held in a liquid or semi-liquid medium facilitating interaction of the two species. The extent of bacterial growth in the presence of the phage is measured by conventional means, preferably by means of an OD reading. Desirably the phage is retained in the selected container, which is conveniently a micro-titer plate, through use of a fixant such as 5% gelatin.

Abstract: Disclosed are bacteria having virulence attenuated by a mutation to the regulatory gene poxR. Also disclosed is a method of producing bacteria having virulence attenuated by mutating to the regulatory gene poxR. Such bacteria are useful for inducing an immune response in an animal or human against virulent forms of the bacteria with reduced risk of a virulent infection. Such bacteria are also useful to allow use of normally virulent bacteria as research tools with reduced risk of virulent infection. In a preferred embodiment, poxR attenuated bacteria can be used as a vaccine to induce immunoprotection in an animal against virulent forms of the bacteria. The disclosed bacteria can also be used as hosts for the expression of heterologous genes and proteins or to deliver DNA for genetic immunization. Attenuated bacteria with such expression can be used, for example, to deliver and present heterologous antigens to the immune system of an animal.

Abstract: Disclosed herein is a modified microorganism which produces an RTX toxin, wherein said RTX toxin is partially or fully inactivated. Also disclosed is a modified microorganism wherein an RTX toxin gene including an RTX structural gene and/or a post-translational activator of the organism is partially or full inactivated. As disclosed, the precursor of an RTX toxin has reduced toxic activity.

Abstract: A polypeptide has first and second domains which enable the polypeptide to be translocated into a target cell or which increase the solubility of the polypeptide, or both, and further enable the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: The present invention is directed to mutant Salmonella sp. having a genetically modified msbB gene in which the mutant Salmonella is capable of targeting solid tumors. The invention is also directed to Salmonella sp. containing a genetically modified msbB gene as well as an genetic modification in a biosynthetic pathway gene such as the purI gene. The present invention further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.

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: Methods and compositions are provided herein for the use 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 a vaccine preparation.

Abstract: The invention provides trpS polypeptides and DNA (RNA) encoding trpS polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing trpS polypeptides to screen for antibacterial compounds.

Abstract: A herpesvirus vaccine comprising a mutated herpesvirus suspended in a pharmaceutically acceptable carrier. The mutated herpesvirus is capable of infecting cells of the mammal to be vaccinated, but incapable of completing a replicative cycle, and it is capable of eliciting a protective immune response in that mammal. The mutated herpesvirus is also capable of treating immunomodulatory or immunoregulatory diseases. The mutation occurs in at least one gene encoding a protein essential for replication of the virus, so that the mutation renders the virus replication defective.

Abstract: A live vaccine of recombinant mutants of a member of the family Pasteurellaceae lacking a rib gene necessary for production of riboflavin as well as a method of vaccination therewith is described. The vaccine is effective against members of the family Pasteurellaceae.

Abstract: Acellular pertussis vaccines comprise purified toxin or toxoid thereof, filamentous haemagglutinin, pertactin and fimbrial agglutinogens formulated to confer protection to at least 70% of members of an at-risk population. The fimbrial agglutinogens may be prepared from a Bordetella strain, particularly a B. pertussis strain, by a multiple step procedure involving extraction of the fimbrial agglutinogens from cell paste and concentrating and purifying the extracted material.

Abstract: The invention provides 76 kDa Helicobacter polypeptides, which can be used in vaccination methods for preventing or treating Helicobacter infection, and polynucleotides that encode these polypeptides.

Abstract: Autologous promoters are used to effect expression of gene products in Bordetella strains. Hybrid Bordetella genes are constructed comprising a Bordetella gene, particularly one encoding a Bordetella antigen, fused at an ATG codon to a native but autologous Bordetella promoter or other Bordetella strain. Genes and promoters from B. pertussis are preferred. B. pertussis, containing the hybrid gene by insertion into the chromosome of the organism by homologous recombination at specific loci, effects expression of the protein for which the Bordetella gene codes at a production rate different from that achieved for the homologous gene. Specific strains and plasmids are described.

Abstract: Recombinant adenoviruses comprising a heterologous DNA sequence coding for glial-derived neurotrophic factor (GDNF), preparation thereof, and use thereof for treating and/or preventing degenerative neurological diseases.

Abstract: The present invention provides an isolated feline calicivirus and mutants thereof, which were isolated from the urine of a cat with lower urinary tract disorder. The present invention further provides nucleic acid clones of the virus, in particular, a clone which encodes the capsid antigen of the virus. The present invention is useful for providing a live or killed virus vaccine comprising the virus or mutants thereof, a subunit vaccine comprising the capsid antigen of the virus, a nucleic acid vaccine encoding the capsid antigen of the virus, and a recombinant virus vector vaccine encoding the capsid antigen of the virus. The present invention also provides a method for isolating feline calicivirus from urine and an assay for diagnosing cats infected with feline calicivirus.

Abstract: Live-attenuated vaccines against Edwardsiella ictaluri or against Pasteurella piscicida are disclosed. Both vaccines are incapable of reversion to virulence, because both are made by deletion mutations in the aroA gene, the purA gene, or both. These vaccines may be used not only to vaccinate fish against Edwardsiella ictaluri or Pasteurela piscicida, but also to serve as vectors to present antigens from other pathogens to the fish, thereby serving as vaccines against other pathogens as well, with no risk of infection by reversion to the virulent form of the pathogen in which the antigen occurs naturally.

Abstract: An isolated and purified outer membrane protein of a Moraxella strain, particularly M. catarrhalis, has a molecular mass of about 200 kDa. The about 200 kDa outer membrane protein as well as nucleic acid molecules encoding the same are useful in diagnostic applications and immunogenic compositions, particularly for in vivo administration to a host to confer protection against disease caused by a bacterial pathogen that produces the about 200 kDa outer membrane protein or produces a protein capable of inducing antibodies in a host specifically reactive with the about 200 kDa outer membrane protein.

Abstract: The present invention relates to an isolated 17-kDa Brucclla antigen characterized by an amino acid sequence having at least 60% homology, preferably at least 70% homology, more preferably having at least 80% homology to the amino acid sequence as shown in SEQ ID No. 1 or 2, with said antigen being specifically recognized by sera from Brucella field infected individuals, more particulary an antigen characterized by the amino acid sequence as shown in SEQ ID No. 1 or 2. The invention also relates to recombinantly produced 17 kDa Brucella antigen, nucleic acids coding for the same and the use thereof in diagnostic and prophylactic methods and kits.

Abstract: A method and vaccine for treatment of pythiosis in humans and animals is described. In particular a vaccine comprising a mixture of extracellular and intracellular proteins is described. The vaccine enables cures of chronic pythiosis in some patients.

Abstract: Methods of preparing recombinant Bacillus anthracis protective antigen or a variant or fragment thereof for use in vaccines is disclosed. The protein is expressed in a recombinant microorganism which comprises a sequence which encodes PA or said variant or fragment thereof wherein either (i) a gene of the microorganism which encodes a catabolic repressor protein and/or AbrB is inactivated, and/or (ii) wherein a region of the PA sequence which can act as a catabolic repressor binding site and/or an AbrB binding site is inactivated. Useful quantities of protein are obtainable from these organisms.

Abstract: The invention provides ribB polypeptides and polynucleotides encoding ribB polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing ribB polypeptides to screen for antibacterial compounds.

Abstract: The invention provides nusB polypeptides and polynucleotides encoding nusB polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nusB polypeptides to screen for antibacterial compounds.

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. The conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.

Abstract: V. cholerae vaccine strains which have a soft agar penetration-defective phenotype and methods for making such strains are described. Also described are methods for identifying new genes involved in V. cholerae motility and the cloning, identification, and sequencing of V. cholerae motB and fliC genes.

Abstract: The present invention is directed to compositions and methods for the production for the prevention of disease due to P. haemolytica. In particular, the present invention provides P. haemolytica strains that produce inactive leukotoxin for vaccine and other uses. The present invention also provides compositions and methods for genetic manipulations in P. haemolytica.