Abstract: A transcutaneous immunization system delivers antigen to immune cells without perforation of the skin, and induces an immune response in an animal or human. The system uses an adjuvant, preferably an ADP-ribosylating exotoxin, to induce an antigen-specific immune response (e.g., humoral and/or cellular effectors) after transcutaneous application of a formulation containing antigen and adjuvant to intact skin of the animal or human. The efficiency of immunization may be enhanced by adding hydrating agents (e.g., liposomes), penetration enhancers, or occlusive dressings to the transcutaneous delivery system. This system may allow activation of Langerhans cells in the skin, migration of the Langerhans cells to lymph nodes, and antigen presentation.

Abstract: This invention relates to conjugates of the O-specific polysaccharide of E. coli O157 with a carrier, and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in mammals, including responses which provide protection against, or reduce the severity of, bacterial infections. More particularly it relates to the use of polysaccharides containing the tetrasaccharide repeat unit: (?3)-?-D-GalpNAc-(1?2)-?-D-PerpNAc-(1?3)-?-L-Fucp-(1?4)-?-D-Glcp-(1?), and conjugates thereof, to induce serum antibodies having bactericidal (killing) activity against hemolytic-uremic syndrome (HUS) causing E. coli, in particular E. coli O157. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies which have bactericidal or bacteriostatic activity against against E. coli, in particular E. coli O157, and are useful to prevent and/or treat illnesses caused by E. coli O157.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: Immunologically active polypeptides with no or reduced toxicity useful for the preparation of an antipertussis vaccine. Method for the preparation of said polypeptides which comprises, cultivating, a microorganism transformed with a hybrid plasmid including the gene/s which codes for at least one of said polypeptides in a suitable medium and recovering the desired polypeptide from the cells or from the culture medium.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: The invention relates to an immunogenic composition, characterized in that it comprises an adenyl cyclase-hemolysin (AC-Hly) protein, or an immunogenic portion of this AC-Hly, of a strain of Bordetella chosen from B. pertussis, B. parapertussis or B bronchiseptica, and in that it comprises, in addition, a bacterial extract containing the expression products of the vrg genes of a strain of Bordetella chosen from B. pertussis, B. parapertussis or B bronchiseptica, or a portion of these expression products which is sufficient to induce an immune response in a host to which the extract might be administered.

Abstract: The invention provides the use of an antigen which is a mucosally immunogenically active substance comprising the 50 kD C fragment of tetanus toxin, an immunogenic fragment thereof, or a derivative thereof formed by amino acid deletion, substitution or insertion for the manufacture of a vaccine composition for administration to a mucosal surface to induce an immune response in the mucosal surface against tetanus infection. The Vaccine composition preferably contains the P.69 outer membrane protein of B. pertussis, and B. pertussis filamentous haemaglutiuin. The invention also provides vaccine compositions per se and a method of treating tetanus and optionally whooping cough using the vaccine compositions.

Abstract: The present invention is directed to vaccine compositions and methods for immunizing poultry. The vaccine compositions comprise inactivated bacterial organisms which can be administered to the poultry through oral intake of water.

Abstract: Compositions characterized by ADP-ribosyltransferase activity are useful in promoting prophylactic and/or therapeutic responses as are promoted by, e.g., pertussis toxin but directed against another target antigen (e.g., a cancer-related antigen) in a mammalian patient.

Abstract: Pertactin (PRN) is an outer membrane protein expressed by Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica, which induces protective immunity to Bordetella infections. The immunodominant and immunoprotective epitopes of pertactin include two repeated regions, I and II. Comparison of these two repeated regions showed the pertactin of B. parapertussis is invariant, whereas the pertactin of B. pertussis varies mostly in region I and B. bronchiseptica varies in both the repeated regions I and II. Compositions containing pertactins and pertactin fragments containing variant sequences in these regions are useful as immunogenic compositions.

Abstract: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animal cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the a patients body may be provided while release of detergents included in the many liposome preparation protocols may be avoided.

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: 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: This invention relates to hepatitis B virus (“HBV”) core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them.

Abstract: A variety of different types of nasal vaccine systems have been described including cholera toxin, microspheres, nanoparticles, liposomes, attenuated virus, and outer membrane proteins (proteosomes). The present invention is directed toward a novel nasal vaccine composition that utilizes the cationic polysaccharide, chitosan, as a delivery system. Chitosan is a polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine. The term chitosan encompasses a series of chitosan polymers with different molecular weights (50 kDa-2,000 kDa) and degree of acetylation (40%-98%). Several vaccine animal studies were carried out employing influenza or pertussis antigens in combination with chitosan. Nasal administration of chitosan-antigen nasal vaccines induced significant serum IgG responses and secretory IgA levels. Animals vaccinated via the nasal route with various chitosan-antigen vaccines were also found to be protected against the appropriate challenge.

Abstract: The invention relates to an immunogenic composition, characterized in that it comprises an adenyl cyclase-hemolysin (AC-Hly) protein, or an immunogenic portion of this AC-Hly, of a strain of Bordetella chosen from B. Tertussis, B. parapertussis or B. bronchiseptica, and in that it comprises, in addition, a bacterial extract containing the expression products of the vrg genes of a strain of Bordetella chosen from B. pertussis, B. parapertussis or B. bronchiseptica, or a portion of these expression products which is sufficient to induce an immune response in a host to which the extract might be administered.

Abstract: A method for improving the immune response of an animal to a vaccine, comprising: feeding an animal a diet of contamination-resistant feed, and treating said animal with an anti-viral or anti-bacterial vaccine.

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: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animals cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example, catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the patient's body may be provided while release of detergents included in the many lipoome preparation protocols may be avoided.

Abstract: The subject of the invention is amino acid sequences of the AC-Hly from B. pertussis. B. parapertussis and/or B. bronchiseptica, carrying epitopes capable of inducing a protective immune response against infection by Bordetella. The subject of the invention is antibodies, especially monoclonal antibodies, directed against these epitopes.

Abstract: A method for producing a conjugate vaccine includes mixing a uronium salt reagent with a first moiety (e.g., a polysaccharide). According to the invention, the uronium salt reagent has a chemical structure corresponding to formula I: wherein R1 is defined as wherein R6 represents the carbon, hydrogen, and optionally one or more heteroatoms which, together with the nitrogen atom to which they are attached, constitute a 5 to 10 membered heterocyclic ring, which may be substituted or unsubstituted. R2, R3, R4, and R5, each independently represents a hydrogen atom, a substituted or unsubstituted alkyl having 1 to 6 carbon atoms, a substituted or unsubstituted alkenyl having 2 to 6 carbon atoms, or an alkynyl having 2 to 6 carbon atoms. Alternatively, R2 and R3, when taken together, can represent the carbon, hydrogen, sulfur, nitrogen, or oxygen atoms necessary to complete a 5 to 7 membered heterocyclic ring with the nitrogen atom to which they are attached.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule in an amount sufficient to control the aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity. The present invention further makes available methods and reagents for ameliorating the consequences of hedgehog loss-of-function, ptc gain-of-function, or smoothened loss-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule, in an amount sufficient to ameliorate the In certain embodiments, the subject compounds, e.g., a cAMP analog, adenylate cyclase agonist, or cAMP phosphodiesterase inhibitor, regulate cAMP levels, which in turn modulates activity of the hedgehog pathway.

Abstract: The present invention is concerned with a vaccine for combating B. bronchiseptica infection in susceptible animals (such as dogs and swine), containing proteins or polypeptides typical of the fimbrial protein of B. bronchiseptica, or containing recombinant polynucleotides having as part thereof a polynucleotide coding for the protein or polypeptide, and also is concerned with the preparation of said proteins, polypeptides and polynucleotides.

Abstract: The invention relates to the use of an antigen which is a non-toxic double mutant form of pertussis toxin for the manufacture of a vaccine composition for intranasal administration to induce an immune response against B. pertussis infection. The invention also relates to the use of a non-toxic double mutant form of pertussis toxin for the manufacture of an adjuvant composition for stimulating or enhancing a protective immune response of an antigen co-administered therewith. The non-toxic double mutant is preferably one in which the glutamic acid 129 amino acid in the S1 sub-unit has been substituted by glycine and the arginine 9 amino acid has been substituted by lysine.

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 present invention is directed to lectin derived carbohydrate binding peptides or derivatives thereof useful for suppressing inflammatory responses, inducing tolerance to an antigen, and suppressing cell adhesion, e.g., involved in metastasis. In particular, peptides capable of binding terminally linked &agr;-sialic acid(2-6)&bgr;Gal- and/or &agr;-sialic acid(2-3)&bgr;Gal-groups on structures or molecules comprising such groups are provided. Pharmaceutical compositions containing such lectin derived carbohydrate binding peptides are also disclosed.

Abstract: Disclosed are compositions and methods for enhancing the antibody and T cell response to cellular antigens by incorporating an immunopotentiating agent into the cellular membrane or into an intracellular compartment. Such adjuvant-incorporated cell compositions are useful in methods to increase immune responses against antigens, including immunologically cryptic tumor cell antigens, and may be employed to generate useful diagnostic antibodies, to elicit anti-tumor effects in immunized animals, and to significantly prolong survival in animals with cancer.

Abstract: The invention relates to a method for immunizing a mammal against infection by a first Bordetella species. The method comprises administering to the mammal a preparation comprising a portion of the amino acid sequence of mature adenylate cyclase of a second Bordetella species. The invention also relates to vaccine preparations comprising a portion of the amino acid sequence of mature adenylate cyclase from Bordetella species.

Abstract: The present invention provides novel antigenic preparations comprising proteinaceous material associated with adenylate cyclase activity in cultures of B. pertussis, the said preparations being useful as components of acellular whooping cough vaccines. The invention further provides methods for the isolation of such antigenic preparations.