Abstract: The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. The invention also relates to the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. The invention furthermore relates to the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.

Abstract: A vaccine for treating or preventing the establishment of latent tuberculosis infections is provided. The vaccine comprises a recombinant mycobacterium that overexpresses the transcription factor DosR, at a level sufficient to induce production of the dosR regulon genes or proteins. A host to whom the vaccine is administered mounts an immune response to the dosR regulon proteins and is thus protected from the establishment, persistence or reactivation of latent tuberculosis.

Abstract: Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.

Abstract: Recombinant Mycobacterium strains with improved vaccinal properties for use as vaccinating agents are provided. The parent strains of the recombinant Mycobacterium strains are selected for their potent immunogenicity. The Mycobacterium strains do not display antibiotic resistance, and do not exhibit horizontal transfer to gram-negative bacteria.

Abstract: Bacterial packaging strains useful for generating recombinant double-stranded RNA nucleocapsids (rdsRNs) are provided. The packaging strains are useful for the production of RNA encoding vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs in eukaryotic cells or tissues. Recombinant ssRNA is introduced into the strains and packaged to form rdsRNs de novo.

Abstract: We describe a bacterial delivery system for the delivery of DNA and antigens into cells. We constructed an attenuated bacterial vector which enters mammalian cells and ruptures delivering functional plasmid DNA and antigens into the cell cytoplasm. This Shigella vector was designed to deliver DNA to colonic surfaces, thus opening the possibility of oral and other mucosal DNA immunization and gene therapy strategies. The attenuated Shigella is also useful as a vaccine for reducing disease symptoms caused by Shigella.

Abstract: We describe a bacterial delivery system for the delivery of DNA and antigens into cells. We constructed an attenuated bacterial vector which enters mammalian cells and ruptures delivering functional plasmid DNA and antigens into the cell cytoplasm. This Shigella vector was designed to deliver DNA to colonic surfaces, thus opening the possibility of oral and other mucosal DNA immunization and gene therapy strategies. The attenuated Shigella is also useful as a vaccine for reducing disease symptoms caused by Shigella.

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: The present invention is directed to a bacterial delivery system for delivering alphavirus replicon DNA into an animal or animal cells with the replicon encoding one or more heterologous genes to be expressed in the animal or the animal cells. The bacteria are invasive bacteria or attenuated invasive bacteria engineered to contain a DNA vector that encodes the alphavirus replicon in a eukaryotic expression cassette. The heterologous gene can encode an antigen, a therapeutic agent, an immunoregulatory agent, an anti-sense RNA, a catalytic RNA, a protein, a peptide, an antibody or an antigen-binding fragment of an antibody. In a preferred embodiment, the heterologous gene encodes one or more antigens useful as a vaccine for HIV. In addition to the bacterial delivery system, the invention provides methods of introducing and expressing the heterologous gene(s) in animal or animal cells and methods of stimulating or inducing an immune response.

Abstract: The present invention is directed to a bacterial delivery system for delivering alphavirus replicon DNA into an animal or animal cells with the replicon encoding one or more heterologous genes to be expressed in the animal or the animal cells. The bacteria are invasive bacteria or attenuated invasive bacteria engineered to contain a DNA vector that encodes the alphavirus replicon in a eukaryotic expression cassette. The heterologous gene can encode an antigen, a therapeutic agent, an immunoregulatory agent, an anti-sense RNA, a catalytic RNA, a protein, a peptide, an antibody or an antigen-binding fragment of an antibody. In a preferred embodiment, the heterologous gene encodes one or more antigens useful as a vaccine for HIV. In addition to the bacterial delivery system, the invention provides methods of introducing and expressing the heterologous gene(s) in animal or animal cells and methods of stimulating or inducing an immune response.

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: 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: 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: An antibody to tumor necrosis factor-&agr; (anti-TNF) and an antibody to bacterial lipopolysaccharide (anti-LPS) used together in a neutropenic rat model of sepsis are shown to enhance survival of the rats relative to either antibody used alone. Pharmaceutical products including each of the components are therefore of utility in therapy of sepsis. The anti-LPS antibody included may be specific for the O-specific clain of a particular bacterial lipopolysaccharide (serotype specific antibody) but preferably recognizes the core glycolipid of lipopolysaccharide.

Abstract: A method of immunizing against disease caused by Streptococcus pneumoniae is provided in which children are immunized at age 2 and again at age 4 months with a conjugated pneumococcal polysaccharide vaccine. These immunizations are followed by an immunization at 6 months with an unconjugated pneumococcal polysaccharide vaccine. Optionally, a fourth immunization at 12 months with unconjugated pneumococcal polysaccharide vaccine is given.

Abstract: We describe a bacterial delivery system for the delivery of DNA and antigens into cells. We constructed an attenuated bacterial vector which enters mammalian cells and ruptures delivering functional plasmid DNA, such as a mammalian expression plasmid, and antigens into the cell cytoplasm. This Shigella vector was designed to deliver DNA to colonic surfaces, thus opening the possibility of oral and other mucosal DNA immunization and gene therapy strategies. The attenuated Shigella is also useful as a vaccine for reducing disease symptoms caused by Shigella.

Abstract: A method for isolating a non toxic, high molecular weight polysaccharide igen from the crude slime of a Pseudomonas aeruginosa culture, and a method for inducing immunity in a host to said live organisms is described. The slime is initially prepared for the isolation procedure by separating the bacterial cells from the slime and dissolving the slime in a phosphate buffer solution. Dissolved contaminating nucleic acids are then precipitated and separated from solution. A lipid A portion of the contaminating lipopolysaccharide constituent is then removed and precipitated by acetic acid hydrolysis, and the remaining lipids present are extracted with chloroform. Nearly all of the residual nucleic acids are then removed by digestion with nucleases, and the remaining protein extracted with phenol. The aqueous and phenol layers are then separated, and the aqueous layer applied to a gel filter to isolate the antigen by column chromatography. The antigen appears in the void volume.