Abstract: Immununological compositions and methods for making and using them. The compositions contain at least one antigen and at least one lipoprotein and optionally an adjuvant. The lipoprotein can itself be antigenic or immunogenic. The antigen can be influenza HA and the lipoprotein a recombinantly expressed product having an OspA leader for lipidation and PspA for the protein portion. The antigen can be OspC and the lipoprotein OspA. The components of the composition are co-administered. A potentiated immunological response is obtained by the compositions and methods.

Abstract: A method is provided for identifying, isolating, and producing htrB mutants of gram-negative bacterial pathogens. The method comprises mutating the htrB gene of a gram-negative bacterial pathogen so that there is a lack of a functional HtrB protein, resulting in a mutant that lacks one or more secondary acyl chains and displays substantially reduced toxicity as compared to the wild type strain. Also, the present invention provides methods for using a vaccine formulation containing the htrB mutant, or the endotoxin isolated therefrom, to immunize an individual against infections caused by gram-negative bacterial pathogens by administering a prophylactically effective amount of the vaccine formulation.

Abstract: The present invention relates to a microorganism, preferably a bacterial strain, preferably a non-pathogenic strain, preferably a non-invasive strain, preferably a food grade strain, preferably a gram-positive bacterial strain, delivering a trefoil peptide in vivo. Preferably said trefoil peptide is TFF1. The present invention further relates to a method for the delivery of trefoil peptide to the gastro-intestinal tract comprising the administration of such a bacterial strain. The present invention also relates to a pharmaceutical composition comprising a trefoil peptide delivering bacterium as well as methods of treatment of acute gastro-intestinal inflammatory diseases comprising administration of said transformed bacterial strains, particularly for treating acute colitis, including but not limited to acute flare-ups of Crohn's disease and ulcerative colitis in humans, as well as for treating gastro-intestinal disorders of a similar nature in other animal species.

Abstract: The present invention discloses development of a model live vaccine for HIV, using an attenuated strain of Salmonella engineered to surface express specific HIV proteins and testing of this vaccine in mice. There are provided two recombinant plasmids, containing the Lpp-OmpA genes required for surface exposure, followed by the genes for the HIV-1 proteins, Reverse Transcriptase or Transactivating protein (Tat). These plasmids are electroporated into an attenuated strain of Salmonella, and antigen expression is verified. These live vaccines are then used to orally inoculate mice and the vaccinated mice are tested for fecal IgA response and helper T cell response specific for the HIV antigens.

Abstract: An isolated peptide fragment of the VapA protein that binds antibodies specific for Rhodococcus equi and the VapA protein. In a preferred form the peptide contains an amino acid sequence of 5 or more amino acid residues that is identical to or homologous to the amino acid sequence of at least one region of the VapA protein that is responsible for immunological recognition. Methods of diagnosing a vertebrate for the presence of R. equi using the peptide and methods of vaccinating a vertebrate against R. equi using the peptide are also claimed.

Abstract: Mycobacterium strains in which the erp gene is modified, and vaccine compositions comprising such Mycobacterium strains are provided. The modification of the erp gene may decrease the virulence and the persistence of the Mycobacterium strains.

Abstract: Methods and vaccines for suppressing formation of or inhibiting growth of tumors in a host are provided, via administration of a vaccine containing either a fusion protein of the tumor associated antigen fused to a truncated form of listeriolysin or a recombinant form of Listeria monocytogenes which grows and spreads and is capable of expressing the tumor associated antigen alone or as a listeriolysin fusion protein.

Abstract: The invention relates to Streptococcus suis infection in pigs, vaccines directed against those infections and tests for diagnosing Streptococcus suis infections. The invention provides an isolated or recombinant nucleic acid encoding a capsular gene cluster of Streptococcus suis or a gene or gene fragment derivated thereof. The invention further provides a nucleic acid probe or primer allowing species or serotype-specific detection of Streptococcus suis. The invention also provides a Streptococcus suis antigen and vaccine derived thereof.

Abstract: Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Abstract: The present invention is directed to an attenuated Salmonella comprising a eukaryotic expression vector for delivery of the eukaryotic expression vector to a eukaryotic cell. Delivery may be to eukaryotic cells cultured in vitro or to cells in vivo, such as by oral administration of the attenuated Salmonella comprising the eukaryotic expression vector.

Abstract: The present invention provides a vaccine production strain of Bordetella bronchiseptica that produces a pertussis toxin in high yield. The present invention provides a method for creating a Bordetella bronchiseptica cell line which produces a Bordetella pertussis toxin comprising the steps of introducing a plasmid containing a DNA encoding antibiotic resistance into a Bordetella bronchiseptica strain, selecting for isolates in which the DNA encoding antibiotic resistance is recombinantly incorporated into the chromosome in place of the Bordetella bronchiseptica toxin gene, introducing a plasmid containing DNA encoding subunits of the Bordetella pertussis toxins into the Bordetella bronchiseptica isolates; and, selecting for isolates in which DNA encoding Bordetella pertussis toxin subunit is recombinantly incorporated into the chromosome, the resulting cells producing the Bordetella pertussis toxin.

Abstract: A DNA vaccine effective for inhibiting endothelial cell proliferation comprises a DNA construct operably encoding a vascular endothelial growth factor (VEGF) receptor protein. This invention provides DNA vaccines that encode VEGF receptor-2 (KDR, SEQ ID NO: 2), VEGF receptor-1 (Flt-1, (SEQ ID NO: 4), or Flk-1 (the murine homolog of KDR, SEQ ID NO: 6), DNA sequences SEQ ID NOS: 1, 3, and 5 respectively, as well as methods of using such a DNA vaccine to inhibit vascular endothelial cell proliferation in the tumor micro-environment. Anti-angiogenesis and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: Attenuated immunogenic bacteria having an RpoS+ phenotype, in particular, Salmonella enterica serotype Typhi having an RpoS+ phenotype and methods therefor are disclosed. The Salmonella have in addition to an RpoS+ phenotype, an inactivating mutation in one or more genes which render the microbe attenuated, and a recombinant gene capable of expressing a desired protein. The Salmonella are attenuated and have high immunogenicity so that they can be used in vaccines and as delivery vehicles for genes and gene products. Also disclosed are methods for preparing the vaccine delivery vehicles.

Abstract: Methods and compositions for the treatment of microbial infection, and in particular meningococcal disease, comprise a commensal Neisseria or an extract of a commensal Neisseria. Further methods and compositions comprise conimensal Neisseria which express genes from virulent strains of Neisseria and/or heterologous gene products from non-Neisserial sources. Such compositions are used in vaccine preparations for the treatment of microbial infection.

Abstract: The present invention provides a method of nucleic acid, including DNA, immunization of a host, including humans, against disease caused by infection by a strain of Chlamydia, specifically C. pneumoniae, employing a vector containing a nucleotide sequence encoding full-length, 5?-truncated or 3?-truncated 76 kDa protein of a strain of Chlamydia pneumoniae and a promoter to effect expression of the 76 kDa protein gene in the host. Modifications are possible within the scope of this invention.

Abstract: To provide a novel antigenic protein and a nucleic acid encoding the antigenic protein, which are useful for prophylaxis, treatment and diagnosis of diseases caused by fungi including Candida albicans. An antigenic protein characterized in that the antigenic protein is recognized by antiserum derived from a mammal having Candida albicans-infection resistance; and a nucleic acid encoding an antigenic protein which is recognized by antiserum derived from a mammal having Candida albicans-infection resistance.

Abstract: This invention relates to a novel mycobacterial protein named DES, which appears to share significant amino acid sequence homology with soluble stearoyl-ACP desaturases. The results of allelic exchange experiments, indicate that the des gene may be essential to the survival of mycobacteria. These results coupled with the surface localization, the unique structure of DES, and the fact this antigen is expressed in vivo, and DES protein induces a humoral response in human patients, indicate that the DES protein provides a new target for the design of anti-mycobacterial drugs. This invention provides methods of screening molecules that can inhibit the DES enzyme activity of purified DES protein, in order to identify antibiotic molecules that are capable of inhibiting the growth or survival of mycobacteria.

Abstract: The present invention is drawn to an immunogenic composition comprising OspC polypeptides from Lyme Disease causing Borrelia. In one embodiment, the immunogenic composition of the present invention comprises at least one OspC polypeptide or immunogenic fragment thereof from each of Borrelia burgdorferi OspC families A, B, I and K. In another embodiment, the immunogenic composition of the present invention comprises at least one OspC polypeptide or immunogenic fragment thereof from each of Borrelia afzelii OspC families A and B.

Abstract: The present invention relates to novel vaccines for the prevention or attenuation of infection by Streptococcus pneunoniae. The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of Streptococcus pneumoniae. Antigenic polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention additionally relates to diagnostic methods for detecting Streptococcus nucleic acids, polypeptides and antibodies in a biological sample.

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: Bacteria and in particular pathogenic bacteria are treated in a manner which alters the bacteria's native level or activity of DNA methyltransferase (Dam). The alteration results in a change in the bacteria's native level of methylation of adenine in a GATC tetranucleotide which inhibits virulence of the bacteria. Thus, compounds which inhibit proliferation of bacteria are useful in treating bacterial infections.

Abstract: The present invention relates to antigens of Moraxella, in particular, Moraxella bovis, nucleic acid sequences encoding these antigens and formulations for use in raising an immune response against Moraxella.

Abstract: It is possible to inactivate the early stage of lipid A synthesis of mucosal gram negative bacteria without compromising cell viability. In particular the lpxA gene in N. meningitidis was mutated and resulting lpxA knockout mutants were found to be completely lipopolysaccharide (LPS)-deficient. The major outer membrane proteins (OMPs) were detected in normal amounts. The finding provides important implications for understanding of structure and biogenesis of the outer membrane. On a practical level, the availability of LPS-deficient mutants of pathogenic mucosal bacteria such as N. meningitidis opens up new avenues to vaccine development. It enables easy isolation of endotoxin-free purified proteins, outer membranes or even whole-cell preparations for use in immunisation.

Abstract: The invention concerns bacteria strains, obtained from gram-positive bacteria whereof the genome size is not more than 3.2 Mb, and wherein the HtrA surface protease is inactive. Said strains are useful for expressing exported proteins of interest.

Abstract: A method of inducing a cytotoxic T-lymphocyte (CTL) response to an antigen is disclosed. The method involves delivering the antigen to the lymphatic system of an animal regularly over a sustained period of time using, e.g., an osmotic pump. The method is advantageous over prior art methods for inducing a CTL response in that it does not require repetitive immunizations or the use of adjuvants. The method of the present invention can be used for the induction of CTLs in tumor or infectious disease immunotherapy.

Abstract: Immunological compositions and methods for making and using them. The compositions contain at least one antigen and at least one lipoprotein and optionally an adjuvant. The lipoprotein can itself be antigenic or immunogenic. The antigen can be influenza HA and the lipoprotein a recombinantly expressed product having an OspA leader for lipidation and PspA for the protein portion. The antigen can be OspC and the lipoprotein OspA. The components of the composition are co-administered. A potentiated immunological response is obtained by the compositions and methods.

Abstract: The present invention is based on the identification and characterization of a number of novel M. tuberculosis derived proteins and protein fragments. The invention is directed to the polypeptides and immunologically active fragments thereof, the genes encoding them, immunological compositions such as diagnostic reagents containing the polypeptides.

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: Disclosed herein are methods for inducing an immunological CTL response to an antigen by sustained, regular delivery of the antigen to a mammal so that the antigen reaches the lymphatic system. Antigen is delivered at a level sufficient to induce an immunologic CTL response in a mammal and the level of the antigen in the mammal's lymphatic system is maintained over time sufficient to maintain the immunologic CTL response. Also disclosed is an article of manufacture for delivering an antigen that induces a CTL response in an animal.

Abstract: Novel mycobacterial sulfation pathway proteins and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway protein. The present invention further provides genetically modified mycobacteria having a defect in a sulfation pathway enzyme gene; and immunogenic compositions that include such genetically modified mycobacteria.

Abstract: A series of genes from Pseudomonas aeruginosa and Klebsiella are shown to encode products that are implicated in virulence. The identification of these genes therefore allows attenuated microorganisms to be produced. Furthermore, the genes or their encoded products can be used to identify antimicrobial drugs, diagnostic methods for the identification of a pathogen-associated disease, and in the manufacture of vaccines.

Abstract: The present invention relates to an in vitro method for determining the ability of a vaccine composition which comprises one or more antigens or a nucleic acid molecule which encodes one or more antigens to stimulate a T cell response.

Abstract: The present invention relates to peptide sequences enabling mycobacteria to adhere to host cells (e.g., epithelial cells). More particularly, the invention relates to a mycobacterial heparin-binding haemagglutinin type antigen from M. bovis ECG or M. tuberculosis. The invention also relates to a recombinant peptide sequence enabling mycobacteria to adhere to host cells. The polypeptides can be used to prepare vaccines against mycobacterial infections and for serological diagnosis of mycobacterial infections.

Abstract: The present invention relates to the field of medical immunology and further to pharmaceutical compositions, methods of making and methods of use of vaccines. More specifically this invention relates to recombinant proteins derived from the genes encoding Clostridium difficile toxin A and toxin B, and their use in an active vaccine against C. difficile.

Abstract: The present invention is directed to D-alanine racemase mutants of mycobacterial species. The D-alanine racemase gene (alrA) is involved in the systhesis of D-alanine, a basic component of peptidoglycan that forms the backbone of the bacterial cell wall. The present invention is also directed to methods of making live-attenuated vaccines against pathogenic mycobacteria using such alrA mutants and to the vaccines made according to such methods. The present invention is further directed to use of alrA mutants in methods for screening antimycobacterial agents that are synergistic with peptidoglycan inhibitors. Finally, the present invention is directed to methods to identify new pathways of D-alanine biosynthesis for use in developing new drugs targeting peptidoglycan biosynthesis in mycobacteria and to identify vaccines useful against pathogenic mycobacteria.

Abstract: Compounds and methods for the diagnosis and treatment of Chlamydial infection are disclosed. The compounds provided include polypeptides that contain at least one antigenic portion of a Chlamydia antigen and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Chlamydial infection in patients and in biological samples.

Abstract: The present invention comprises the identification, characterization and sequencing of a gene within the V. anguillarum genome, the mugA gene, a live, attenuated strain of V. anguillarum which comprises a mutated mugA gene, methods of making the strain, vaccines comprising the strain and methods of making such vaccines and administering the vaccines to animals. The invention further comprises vaccines comprised of proteins encoded by the mugA gene, to methods of making such vaccines and administering the vaccines to animals, to vectors comprised of the attenuated strain of V.anguillarum and additional immunizing materials, methods of making the vectors and methods of administering the vectors to animals. Also disclosed are probes, passive vaccines and monoclonal antibodies for the detection and prevention of vibriosis.

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: A protein from M. catarrhalis, designated the 74 kD protein, is isolated and purified. The 74 kD protein has an amino-terminal amino acid sequence which is conserved among various strains of M. catarrhalis. The protein has a molecular weight of approximately 74.9 kD as measured on a 10% SDS-PAGE gel, while its molecular weight as measured by mass spectrometry is approximately 74 kD. The 74 kD protein is used to prepare a vaccine composition which elicits a protective immune response in a mammalian host, to protect the host against disease caused by M. catarrhalis.

Abstract: A method is provided for identifying, isolating, and producing htrB mutants of gram-negative bacterial pathogens. The method comprises mutating the htrB gene of a gram-negative bacterial pathogen so that there is a lack of a functional HtrB protein, resulting in a mutant that lacks one or more secondary acyl chains and displays substantially reduced toxicity as compared to the wild type strain. Also, the present invention provides methods for using a vaccine formulation containing the htrB mutant, or the endotoxin isolated therefrom, to immunize an individual against infections caused by gram-negative bacterial pathogens by administering a prophylactically effective amount of the vaccine formulation.

Abstract: The present invention relates to a broadly reactive vaccine against Gram-negative bacteria which is composed of a biological glycan-pilus conjugate. The conjugate core is a common pilus type to which is attached the glycan of choice in vivo. Pooling of these bioconjugates produces a multivalent vaccine. These pili give high bronchial titers when delivered by the intranasal route. Mice vaccinated with pure glycosylated P. aeruginosa strain 1244 pili in this manner are protected against respiratory challenge with P. aeruginosa strain 1244. The present invention further relates to a DNA and amino acid sequence of a new gene, pilO, which is capable of glycosylating pilin of Gram-negative bacteria and uses thereof.

Abstract: A method of delivering a protein to domestic poultry by administering to the poultry by whole body spray an effective amount of a live avirulent derivative of an enteropathogenic bacterium that contains a recombinant gene encoding the protein.

Abstract: Novel mycobacterial sulfation pathway proteins and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway protein. The present invention further provides genetically modified mycobacteria having a defect in a sulfation pathway enzyme gene; and immunogenic compositions that include such genetically modified mycobacteria.

Abstract: The present invention thus provides a polypeptide capable of forming a structure corresponding to or mimicking the intermediate of gp41 as well as its use in a vaccine for treating or preventing HIV infections.

Abstract: Novel mycobacterial sulfation pathway enzymes and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway enzyme.

Abstract: The present invention provides methods of inducing immune responses by recombinant antigen-enterotoxin chimeric mucosal immunogens that contain the A2/B subunits of cholera toxin or heat-labile type II toxins. These chimeric immunogens differentially enhance antibody secretion, cytokine production, as well as B7-dependent co-stimulation of T cells and CD40L expression on CD4+ T cells.

Abstract: Immunization formulations comprising an antigen and an emulsan or emulsan analog are formed and can be administered to a host. The emulsan or emulsan analog is an adjuvant in the immunization formulation. The emulsan or emulsan analog is secreted from Acinetobacter calcoaceticus. In particular, the emulsan or emulsan analog is secreted from Acinetobacter calcoaceticus RAG-1. The emulsan analog is produced and secreted from Acinetobacter calcoaceticus cultured in the presence of varying fatty acid sources. The emulsan analog is also produced and secreted from mutants of Acinetobacter calcoaceticus, such as transposon mutants of Acinetobacter calcoaceticus RAG-1.

Abstract: This invention provides immunogenic compositions containing attenuated bacteria (such as Salmonella enterica) which are resistant to the antimicrobial actions of human defensins, particularly human defensin 5 (HD-5). Methods for using these compositions to elicit a sustained and highly specific immune response are provided. The invention also provides methods for preparing vaccines wherein a heterologous antigen is expressed by the defensin-resistant bacteria.

Abstract: The present invention provides methods for modulating angiogenesis by administering anti-angiogenic Ang-7 polypeptides to a subject. Methods of modulating angiogenesis by administering an anti-angiogenic ANG-7 nucleic acid are also provided.

Abstract: This invention is directed to mutant SPE-C toxins or fragments thereof, vaccine and pharmaceutical compositions, and methods of using the vaccine and pharmaceutical compositions. The preferred SPE-C toxin has at least one amino acid change and is substantially non-lethal compared with the wild type SPE-C toxin. The mutant SPE-C toxins can form vaccine compositions useful to protect animals against the biological activities of wild type SPE-C toxin.