Abstract: This invention relates to the identification, cloning, sequencing and characterization of the iniB, iniA and iniC genes of mycobacteria which are induced by a broad class of antibiotics that act by inhibiting cell wall biosynthesis, including the first line antituberculosis agents, isoniazid and ethambutol. The present invention provides purified and isolated iniB, iniA, iniC and iniB promoter nucleic acids which may comprise the iniBAC operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the iniB, iniA, iniC and iniB promoter nucleic acids, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the screening and identification of drugs effective against Mycobacterium tuberculosis using induction of the iniB promoter.

Abstract: The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp 120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes.

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: This invention relates to the identification, cloning, sequencing and characterization of the iniB, iniA and iniC genes of mycobacteria which are induced by a broad class of antibiotics that act by inhibiting cell wall biosynthesis, including the first line antituberculosis agents, isoniazid and ethambutol. The present invention provides purified and isolated iniB, iniA, iniC and iniB promoter nucleic acids which may comprise the iniBAC operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the iniB, iniA, iniC and iniB promoter nucleic acids, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the screening and identification of drugs effective against Mycobacterium tuberculosis using induction of the iniB promoter.

Abstract: The method provided by the present invention sets forth a novel combination of methods and principles which allows for the rapid and accurate isolation and identification of a large number of differentially expressed mRNAs.

Abstract: The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes.

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: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: The method provided by the present invention sets forth a novel combination of methods and principles which allows for the rapid and accurate isolation and identification of a large number of differentially expressed mRNAs.

Abstract: This invention relates to mycobacterial species-specific reporter mycobacteriophages (reporter mycobacteriophages), methods of producing said reporter mycobacteriophages and the use of said reporter mycobacteriophages for the rapid diagnosis of mycobacterial infection and the assessment of drug susceptibilities of mycobacterial strains in clinical samples. In particular, this invention is directed to the production and use of luciferase reporter mycobacteriophages to diagnose tuberculosis. The mycobacterial species-specific reporter mycobacteriophages comprise mycobacterial species-specific mycobacteriophages which contain reporter genes and transcriptional promoters therein. When the reporter mycobacteriophages are incubated with clinical samples which may contain the mycobacteria of interest, the gene product of the reporter genes will be expressed if the sample contains the mycobacteria of interest, thereby diagnosing mycobacterial infection.

Abstract: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: This invention relates to the identification, cloning, sequencing and characterization of the iniB, iniA and iniC genes of mycobacteria which are induced by a broad class of antibiotics that act by inhibiting cell wall biosynthesis, including the first line antituberculosis agents, isoniazid and ethambutol. The present invention provides purified and isolated iniB, iniA, iniC and iniB promoter nucleic acids which may comprise the iniBAC operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the iniB, iniA, iniC and iniB promoter nucleic acids, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the screening and identification of drugs effective against Mycobacterium tuberculosis using induction of the iniB promoter.

Abstract: This invention relates to mycobacterial species-specific reporter mycobacteriophages (reporter mycobacteriophages), methods of producing said reporter mycobacteriophages and the use of said reporter mycobacteriophages for the rapid diagnosis of mycobacterial infection and the assessment of drug susceptibilities of mycobacterial strains in clinical samples. In particular, this invention is directed to the production and use of luciferase reporter mycobacteriophages to diagnose tuberculosis. The mycobacterial species-specific reporter mycobacteriophages comprise mycobacterial species-specific mycobacteriophages which contain reporter genes and transcriptional promoters therein. When the reporter mycobacteriophages are incubated with clinical samples which may contain the mycobacteria of interest, the gene product of the reporter genes will be expressed if the sample contains the mycobacteria of interest, thereby diagnosing mycobacterial infection.

Abstract: The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes.

Abstract: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: This invention is directed to a method for stimulating, the proliferation of V.gamma.2V.delta.2 T cells comprising contacting V.gamma.2V.delta.2 T cells with a V.gamma.2V.delta.2 T cell proliferation stimulating amount of a compound selected from the group-consisting of a monoalkyl phosphate, a hydroxy monoalkyl phosphate, a carboxy monoalkyl phosphate, a monoalkyl pyrophosphate, an alkenyl pyrophosphate, a .gamma.-monoalkyl nucleoside triphosphate, a .gamma.-monoalkyl deoxnucleoside triphosphate, a .gamma.-alkenyl nucleoside triphosphate, and a .gamma.-alkenyl deoxynucleoside triphosphate.

Abstract: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: Polynucleotides associated with virulence in mycobacteria, and particularly a fragment of DNA isolated from M. bovis that contains a region encoding a putative sigma factor. Also provided are methods for a DNA sequence or sequences associated with virulence determinants in mycobacteria, and particularly in M. tuberculosis and M. bovis. The invention also provides corresponding polynucleotides associated with avirulence in mycobacteria. In addition, the invention provides a method for producing strains with altered virulence or other properties which can themselves be used to identify and manipulate individual genes.

Abstract: Methods for using reporter mycobacteriophage (RM) and p-nitro-.alpha.-acetylamino-.beta.-hydroxy-propiophenone (NAP) to identify TB complex mycobacteria and distinguish these species from MOTT. RM-infected MOTT show little or no reduction in signal when treated with NAP. In contrast, TB complex mycobacteria infected with RM are distinguishable from RM-infected MOTT by a reduction in signal with NAP treatment.

Abstract: This invention is directed to a method for stimulating the proliferation of V.gamma.2V.delta.2 T cells comprising contacting V.gamma.2V.delta.2 T cells with a V.gamma.2V.delta.2 T cell proliferation stimulating amount of a compound selected from the group consisting of a monoalkyl phosphate and an alkenyl pyrophosphate.