Abstract: This invention pertains in part to a method for delivering functional DNA or antigens. The desired DNA is introduced into attenuated bacteria able to enter cells. Once the bacteria is in the cell, antimicrobial agents are introduced such that they enter the mammalian cell and lyse the bacteria thereby allowing the delivery of carried functional DNA or antigens. The advantages of this method and its uses are described.

Abstract: A host is immunized against infection by a strain of Chlamydia by initial administration of an attenuated bacteria harbouring a nucleic acid encoding a Chlamydia protein followed by administration of a Chlamydia protein in ISCOMs. This procedure enables a high level of protection to be achieved.

Abstract: A salmonella live vaccine produced from at least one attenuated immunologic live vaccine strain, characterized in that the vaccine strain has an envelope marker which results in an increased sensitivity of the vaccine strain toward a specific therapeutically effective antibiotic and has at least one chromosomal antibiotic resistance mutation for the attenuation.

Abstract: High molecular weight surface proteins of non-typeable Haemophilus influenzae which exhibit immunogenic properties and genes encoding the same are described. Specifically, genes coding for two immunodominant high molecular weight proteins, HMW1 and HMW2, have been cloned, expressed and sequenced, while genes coding for high molecular proteins HMW3 and HMW4 have also been cloned, expressed and sequenced.

Abstract: Improved aerodynamically light particles for vaccine delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light vaccine:) are made of a biodegradable material and have a tap density less than 0.4 g/ml and a mass mean diameter between 5 &mgr;m and 30 &mgr;m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear .alpha.-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and it least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light vaccine particles having a large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a vaccine agent to the alveolar region of the lung.

Abstract: The present invention relates to recombinant mycobacteria, particularly recombinant M. bovis, BCG, engineered to express a MUC1 polypeptide and human interleukin-2 for use in cancer immunotherapy.

Abstract: Vaccines and immunotherapeutics for preventing intracellular pathogen diseases in mammals are provided that consist of recombinant attenuated intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens. Exemplary vaccines and immunotherapeutics include attenuated recombinant Mycobacteria expressing the major extracellular non-fusion proteins of Mycobacteria and/or other intracellular pathogens. These exemplary vaccines are shown to produce surprisingly potent protective immune responses in mammals that surpass those of any previously known anti-mycobacterium vaccine. More specifically, a recombinant BCG expressing the 30 kDa major extracellular non-fusion protein of Mycobacterium tuberculosis is provided. Additionally, methods for preventing and treating diseases caused by intracellular pathogens are provided.

Abstract: The invention relates to transformed bacteria of the genus Lactobacillus or Streptococcus, the bacteria having a DNA molecule that includes (1) a nucleotide sequence that encodes a protein allergen and (2) a promoter operably linked to the nucleotide sequence.

Abstract: The disclosure below provides a protein export system for efficiently producing recombinant protein from a host cell. In a preferred embodiment, the protein export system utilizes protein export machinery endogenous to the host bacterium into which the protein export system vector is introduced.

Abstract: A protein from the 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 again disease caused by M. catarrhalis.

Abstract: A chimeric polypeptide encoded by the chimeric gene formed by the DNA sequences that encode the antigenic determinants of four proteins of L. infantum is disclosed. The protein obtained, rLiPO-Ct-Q (pPQI) has a molecular mass of 38 kD with an isoelectric point of 7.37. This chimeric polypeptide is useful for preventing and/or treating leishmaniosis in animals or humans.

Abstract: The invention includes auxotrophic attenuated mutants of Listeria and methods of their use as vaccines.

Abstract: The present invention describes recombinant gp90 envelop protein derived from the equine infectious anemia virus, their corresponding encoding recombinant DNA molecule and the process of production of the recombinant protein produced through genetic engineering techniques, to be used in diagnosis, vaccination or in research.

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 present invention provides isolated polynucleotide molecules comprising a nucleotide sequence encoding the DHFR-TS protein of Neospora which polynucleotide molecules are useful in preparing modified live vaccines against neosporosis, and as diagnostic reagents. The present invention further provides cloning and expression vectors, transformed host cells, substantially purified DHFR-TS proteins and peptide fragments, genetic constructs useful for targeted gene deletion, and vaccine compositions.

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: Prokayrotic FAB I polypeptides and DNA (RNA) encoding such FAB I and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such FAB I for the treatment of infection, such as bacterial infections. Antagonists against such FAB I and their use as a therapeutic to treat infections, such asstaphylococcal infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of FAB I nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding FAB I and for detecting the polypeptide in a host.

Abstract: The present invention is directed towards methods of producing antibodies using an attenuated strain of pathogenic bacteria (e.g. Haemophilus, E. coli, and/or Salmonella) having non-reverting genetic mutations relative to the wild-type organism which alter activity of DNA adenine methylase (Dam). The invention further includes compositions comprised of the attenuated bacteria and methods using these compositions to elicit an immune response and immunize a subject with highly specific antibodies. The invention also provides methods producing antibodies to heterologous antigens which the attenuated bacteria are engineered to produce.

Abstract: Immunogenic compositions are disclosed which are comprised of bacteria which are pathogenic in their native state but which are rendered non-pathogenic in a manner which alters the native level or activity of DNA adenine methylase. The genome is also artificially engineered to express a heterologous antigen such as an immunogenic antigen of a virus, protozoa, parasite or fungi.

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: The present invention is directed towards an attenuated strain of pathogenic bacteria (e.g. Haemophilus, E. Coli, and/or Salmonella) having non-reverting genetic mutations relative to the wild-type organism which alter activity of DNA adenine methylase (Dam). The invention further includes compositions comprised of the attenuated bacteria 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 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: 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: A vaccine for protecting birds against infection by avian pathogenic gram negative microbes is disclosed. The vaccine is a recombinant Salmonella strain expressing O-antigen of an avian pathogenic gram negative microbe such as an E. coli strain that is pathogenic in poultry. The recombinant Salmonella strain also does not express Salmonella O-antigen. Methods of using the vaccine to immunize birds are also disclosed.

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: Novel vaccines for use against &bgr;-hemolytic Streptococcus colonization or infection are disclosed. The vaccines contain an immunogenic amount of a variant of strepococcal C5a peptidase (SCP). Also disclosed is a method of protecting a susceptible mammal against &bgr;-hemolytic Streptococcus colonization or infection by administering such a vaccine. Enzymatically inactive SCP, and polynucleotides encoding these SCP proteins are further disclosed.

Abstract: This invention concerns a recombinant vaccine for the prevention of mastitis in milking mammals, particularly cows, and to methods for the production and use of the vaccine. The vaccine against mastitis is made from an E. coli cell that has been genetically engineered, or transformed, to contain and express an antigen from one or more of the pathogens responsible for causing mastitis.

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: Methods and compositions for the prevention and diagnosis of Lyme disease. OspA and OspB polypeptides and serotypic variants thereof, which elicit in a treated animal the formation of an immune response which is effective to treat or protect against Lyme disease as caused by infection with Borrelia burgdorferi. Anti-OspA and anti-OspB antibodies that are effective to treat or protect against Lyme disease as caused by infection with B. burgdorferi. A screening method for the selection of those OspA and OspB polypeptides and anti-OspA and anti-OspB antibodies that are useful for the prevention and detection of Lyme disease. Diagnostic kits including OspA and OspB polypeptides or antibodies directed against such polypeptides.

Abstract: A multi-component immunogenic composition confers protection on an immunized host against infection caused by Haemophilus influenzae. Such composition comprises at least three different antigens of Haemophilus influenzae, two of which are adhesins. High molecular weight (HMW) proteins and Haemophilus influenzae adhesin (Hia) proteins of non-typeable Haemophilus influenzae comprise the adhesin components while the other antigen is a non-proteolytic analog of Hin47 protein. Each component does not impair the immunogenicity of the others. The Haemophilus vaccine may be combined with DTP component vaccines, which may contain inactivated poliovirus, including type 1, type 2 and/or type 3, and/or a conjugate of a capsular polysaccharide of Haemophilus influenzae and tetanus or diphtheria toxoid, including PRP-T, to provide a multi-valent component vaccine without impairment of the immunogenic properties of the other antigens.

Abstract: Mycobacterium tuberculosis protein having a molecular weight of 28.779 Da, and hybrid proteins containing at least portions of its sequence. These proteins may in particular be used in vaccines or for the detection of specific tuberculosis antibodies.

Abstract: Recombinant production of Hia protein, in full-length and N-terminally truncated forms, of non-typeable strains of Haemophilus influenzae, is described. The nucleic acid and deduced amino acid sequences of Hia genes of various strains of non-typeable and type c Haemophilus influenzae also are described.

Abstract: Methods and vaccines for protection of animals against Campylobacter infection are provided.

Abstract: A method of inhibiting, moderating or diagnosing Pseudomonas aeruginosa infection is disclosed. In one embodiment, this method comprises inoculating a patient with an effective amount of PcrV antigen.

Abstract: This invention provides recombinant mycobacterium strains of pathogenic origin that have been attenuated by the inactivation of a gene coding for a metabolic protein, specifically a gene coding for a protein necessary for the biosynthesis of a purine or a pyrimidine base, and more precisely, the purC gene that codes for an enzyme of the metabolic pathway of purine biosynthesis. The recombinant mycobacterium of this invention have a reduced capacity to propagate in a mammalian host, but remain viable in the host for a period of time sufficient to induce an protective immune response against the natural pathogenic mycobacterium counterpart.

Abstract: Disclosed are novel recombinant mutant strains of mycobacteria that are deficient for the synthesis or transport of dimycoserosalphthiocerol (“DIM”). The present invention also provides a method of producing a recombinant mutant mycobacterium that is deficient for the synthesis or transport of DIM, comprising mutating a nucleic acid responsible for the synthesis or transport of dimycoserosalphthiocerol, including a nucleic acid comprising the promoter for the pps operon, fadD28 or mmpL7. The present invention also provides a vaccine comprising a DIM mutant mycobacterium of the present invention, as well as a method for the treatment or prevention of tuberculosis in a subject using the vaccine.

Abstract: The present invention encompasses methods of preparing a recombinant viral vector, within a procaryotic cell, by intermolecular homologous recombination, methods of preparing an infectious viral particle containing the recombinant viral vector and pharmaceutical compositions comprising the vector or particle. The invention also encompasses the therapeutic use of the vector or particle, especially in human gene therapy.

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: This invention provides recombinant mycobacterium strains of pathogenic origin that have been attenuated by the inactivation of a gene coding for a metabolic protein, specifically a gene coding for a protein necessary for the biosynthesis of a purine or a pyrimidine base, and more precisely, the purC gene that codes for an enzyme of the metabolic pathway of purine biosynthesis. The recombinant mycobacterium of this invention have a reduced capacity to propagate in a mammalian host, but remain viable in the host for a period of time sufficient to induce an protective immune response against the natural pathogenic mycobacterium counterpart.

Abstract: A non-virulent, recA defective mutant of Porphyromonas gingivalis. The Porphyromonas gingivalis strain which is deposited at ATCC under accession number 202109. Also a method of decreasing the growth rate or reproduction rate of Porphyromonas gingivalis in a mammal comprising the step of administering to the mammal at least one dose of Porphyromonas gingivalis according to the present invention. Further, a method of preventing or treating a Porphyromonas gingivalis infection such as periodontitis in a mammal comprising the step of administering to the mammal at least one dose of Porphyromonas gingivalis according to the present invention. Also, a pharmaceutical composition comprising a non-virulent, recA defective mutant of Porphyromonas gingivalis.

Abstract: The present invention relates to a genetic engineering process for the optimal production and exposure to the immune system of additional antigen coded for by a live vaccine. The genetic engineering process is based on the use of spontaneous DNA reorganisation in the recombinant live vaccine, such that the recombinant live vaccine spontaneously divides into two subpopulations (A and B), whereby subpopulation A is capable of infecting and acts immunogenically per se as a minimum characteristic and subpopulation B as a minimum characteristic is regenerated by subpopulation A, produces additional antigen and acts immunogenically with respect to said additional antigen.

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: Immunological compositions and methods for making and using them. The compositions contain an antigen and a lipoprotein and optionally an adjuvant. The lipoprotein can itself be antigenic or immurogenic. 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: Injectable water-in-oil emulsion possessing immunity adjuvant activity and which can be used in man and animals as vaccine or an immunological medicament comprising an oily phase comprising an oil , an aqueous phase and at least one emulsifier, wherein the oil of said oily phase is a substantially metabolizable oil or a mixture of substantially metabolizable oils and said emulsifiers or emulsifiers providing with said metabolizable oil a stable emulsion having immunity adjuvant activity and a viscosity of less than 400 mPa.s at 25° C.

Abstract: The present invention relates generally to modified microorganisms suitable for use as live in ovo vaccines for avian species. The live in ovo vaccines of the present invention are useful for inducing immunity before or immediately after hatching against a virulent form of the modified microorganism or a microorganism immunologically related to the modified microorganism or a virulent organism or virus carrying an antigenic determinant expressed by the modified microorganism in the live vaccine. The subject live in ovo vaccines are particularly efficacious in enhancing the survival rate of newly-hatched poultry birds.

Abstract: Compounds and methods are provided for diagnosing Trypanosoma cruzi infection. The disclosed compounds are polypeptides, or antibodies thereto, that contain one or more epitopes of T. cruzi antigens. The compounds are useful in a variety of immunoassays for detecting T. cruzi infection. The polypeptide compounds are further useful in vaccines and pharmaceutical compositions for inducing protective immunity against Chagas' disease in individuals exposed to T. cruzi.

Abstract: The invention relates to the nucleic acid sequence and amino acid sequence of dihydrofolate reductase (DHFR) from mycobacteria and to expression of recombinant DHFR protein. Utilizing the recombinant protein, novel therapies and diagnostic strategies can be developed and selective antimycobacterial compositions can be designed and utilized to treat mycobacterial infections in patients. This invention includes all or portions of novel recombinant nucleic acids encoding DHFR for mycobacteria such as M. avium, to novel recombinant DHFR peptides produced by such sequences, and to vaccines, diagnostic kits, cells and therapies utilizing these peptides and nucleic acid sequences. The present invention relates to methods for using the sequences of the present invention to develop drugs specific to M. avium and other mycobacteria, to identify and sequence corresponding sequences in species other than M. avium, as well as diagnostic and treatment methods incorporating the disclosed sequences and peptides.

Abstract: The present invention refers in general to novel recombinant mycobacteria that are auxotrophic for diaminopimelate. In particular, this invention relates to novel auxotrophic recombinant mycobacteria, to methods of making the mycobacteria, and to uses of the mycobacteria to deliver vaccines. This invention also provides for uses of the mycobacteria in drug screening processes.

Abstract: The invention provides a nucleic acid encoding the 37-kDa protein from Streptococcus pneumoniae. Also provided are isolated nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are antibodies which selectively binds the polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are vaccines comprising immunogenic polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein.

Abstract: Murine monoclonal antibodies directed against a novel outer membrane protein (OMP) of Haemophilus influenzae have been isolated and characterized. The gene encoding of the outer membrane protein has also been isolated and characterized. Portions of the DNA sequence of the 15 kD OMP gene are useful as probes to diagnose the presence of Haemophilus influenzae in samples. These DNA's also make available polypeptide sequences of immunoreactive epitopes encoded within the gene, thus permitting the production of polypeptides which are useful as standards or reagents in diagnostic tests and/or as components of vaccines. Monoclonal antibodies directed against epitopes of the 15 kD OMP are also useful for diagnostic tests and as therapeutic agents for passive immunization.