Abstract: Certain embodiments of the invention provide a formulation suitable for nasal administration comprising water, a prodrug of a therapeutic agent, and an enzyme that is suitable for intranasal conversion of the prodrug to the therapeutic agent, as well as methods of use thereof.

Abstract: The disclosure features vaccine adjuvants comprising prokaryotic mRNA, and methods of vaccination using the adjuvants. More specifically, the disclosure provides a vaccine composition comprising a nonviable immunogen (e.g., heat-killed bacterium), a tumor antigen, or an immunogenic peptide of microbial or mammalian origin, and an adjuvant, wherein adjuvant comprises prokaryotic mRNA (e.g., bacterial mRNA), as well as the methods of using the vaccine compositions. Further disclosed are the structural features of the prokaryotic mRNA used as the adjuvants.

Abstract: The present invention comprises the discovery and development of an effective cryoprotectant composition, without containing skim milk or any other animal-derived compounds, to achieve long-term stability of freeze-dried lactic acid bacteria (LAB), at different temperatures, whereby the retention of viability of the freeze-dried LAB after 6 months of storage, preferably after 9 months of storage, more preferably after 12 months of storage is more than 50%. The invention is in the field of producing freeze dried bacteria, in particular Lactic acid bacteria. More in particular, the invention relates to the use of a novel combination of cryoprotectants for increasing the viability of bacteria after freeze drying, improving the texture of the lyofilized cake for easy grinding and improving the long term stability of the freeze dried bacteria at different temperature conditions. The invention further relates to such freeze dried bacteria for use in food industry or in human or animal health applications.

Abstract: An isolated protein or peptide selected from the group consisting of Bordetella colonization factor A (BcfA) protein and antigenic fragments thereof is described, along with an isolated nucleic acid encoding the same, antibodies that bind to the same, methods of producing an immune response in a mammalian subject in need thereof by administering the proteins, peptides or antibodies, and pharmaceutical compositions comprising the same.

Abstract: An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.

Abstract: Various improvements to vaccines that include a serogroup C meningococcal conjugate antigen, including: (a) co-administration with acellular B. pertussis antigen; (b) co-administration with an inactivated poliovirus antigen; (c) supply in a kit together with a separate pneumococcal conjugate component, which may be in a liquid form; and (d) use in combination with a pneumococcal conjugate antigen but without an aluminum phosphate adjuvant. A kit may have: (a) a first immunogenic component that comprises an aqueous formulation of a conjugated capsular saccharide from Streptococcus pneumoniae; and (b) a second immunogenic component that comprises a conjugated capsular saccharide from Neisseria meningitidis serogroup C.

Abstract: The present invention relates to immunogenic compositions for modulating the immune system, comprising a therapeutically effective quantity of two or more immuno-active antigenic agents with pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs) and one or more physiologically acceptable carriers, excipients, diluents or solvents. The immunogenic compositions according to the present invention are used for producing medicaments for preventing and/or treating, and for preventing and/or treating infectious diseases, auto-immune diseases, allergic diseases, inflammation, arthritis, inflammatory diseases, transplant rejection, affections caused by vascular disorders, diseases caused by haemorrhagic or ischaemic cardiovascular accidents, ischaemia, heart attack and haemorrhagia leading to tissue destruction, heart, kidney, respiratory or liver insufficiency, cancer, malign and benign tumours and neoplasia.

Abstract: Provided herein are compositions, combinations, and methods comprising Bordetella bronchiseptica and isolated pertactin, which are effective in treating or preventing respiratory infections, such as kennel cough, in animals.

Abstract: The invention provides BASB232 polypeptides and polynucleotides encoding BASB232 polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are diagnostic, prophylactic and therapeutic uses. The invention further provides immunogenic compositions comprising a plurality of antigens selected from at least two different categories of antigen, having different functions within Bordetella. Examples of such categories of antigen are autotransporter proteins, iron acquisition proteins, lipoproteins, adhesins and toxins/invasins.

Abstract: The present invention pertains to vaccines suitable for administering systemically that comprise live aro mutant bacteria, an adjuvant, an aromatic supplement, or both an adjuvant and an aromatic supplement. The present invention also pertains to the manufacture of such a vaccine and a method of protecting an animal by administration of the vaccine.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a cancer cell. Delivery of the cargo compound is accomplished by the use of protein transduction domains derived from cupredoxins. The invention further discloses methods for treating cancer and diagnosing cancer.

Abstract: An objective of the present invention is to provide a whole-cell bacterial vaccine composition for preventing whooping cough caused by Bordetella parapertussis, comprising whole cells, whole-cell homogenate, or cell lysate of B. parapertussis as an immunogen, and methods for producing them.

Abstract: Methods and compositions are provided herein for immunizing a subject against Chlamydial genital infection by administering to the subject an effective amount of a Chlamydial immunogenic peptide or an immunogenic fragment or variant thereof incorporated within a vault-like particle carrier. In some aspects, the vault-like-particles are administered to the nasal mucosa. The methods and compositions advantageously exhibit enhanced ability to induce cell-mediated immunity and/or antibody-based immunity at mucosal surfaces while reducing inflammation associated with Chlamydia infection.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a cancer cell. Delivery of the cargo compound is accomplished by the use of protein transduction domains derived from cupredoxins. The invention further discloses methods for treating cancer and diagnosing cancer.

Abstract: The invention relates to process for the preparation of formulations comprising a microorganism Mycobacterium w for the management of bronchial Asthma (obstructive lung disease).

Abstract: Disclosed are dosage forms and related methods, that include a first population of synthetic nanocarriers that have one or more first antigens coupled to them, one or more second antigens that are not coupled to the synthetic nanocarriers, and a pharmaceutically acceptable excipient.

Abstract: The current invention provides new Gram negative polypeptides exhibiting lipid A 3-O-deacylase activity and are capable of modifying and/or detoxifying gram negative LPS. The present invention also provides Gram negative bacteria, Gram negative bacterial lipopolysaccharides (LPS) and compositions comprising LPS, which are provided with or treated with a 3-O-deacylase activity according to the invention and which may be used for pharmaceutical and/or veterinary purposes, in particular for the preparation of whole cell or acellular vaccines against pathogenic Gram negatives such as Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.

Abstract: The invention relates to vaccine compositions comprising chitosan and a vaccine which are administered to avian species via the ocular route, and methods or programs of vaccination including use of chitosan in order to increase or enhance cell-mediated immunity in avian species and persistence of the vaccine avian tissues.

Abstract: An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.

Abstract: An isolated protein or peptide selected from the group consisting of Bordetella colonization factor A (BcfA) protein and antigenic fragments thereof is described, along with an isolated nucleic acid encoding the same, antibodies that bind to the same, methods of producing an immune response in a mammalian subject in need thereof by administering the proteins, peptides or antibodies, and pharmaceutical compositions comprising the same.

Abstract: The present invention provides non-toxic Gram-negative bacteria. In particular, the present invention provides viable Gram-negative bacteria (e.g., E. coli) substantially lacking lipopolysaccharide (LPS, endotoxin) within the outer membrane. The present invention further provides methods of generating viable non-toxic Gram-negative bacteria and uses thereof. The present invention also provides compositions and methods for inducing immune responses and for researching and developing therapeutic agents.

Abstract: The present disclosure relates to multivalent immunogen compositions for treating or preventing diseases or disorders in canines caused by or associated with one or more of canine distemper virus, canine adenovirus (type 1 or type 2), canine parainfluenza virus, canine parvovirus, Leptospira canicola, Leptospira icterohaemorrhagiae, Leptospira grippotyphosa, Leptospira pomona, Leptospira bratislava, Leptospira hardjo, Leptospira autumnalis, Leptospira australis, Leptospira hebdomadis, and Bordetella bronchiseptica. The Leptospira compositions can also be used for treating or preventing leptospirosis diseases or disorders in canine, swine, and bovine.

Abstract: A canine respiratory coronavirus (CRCV) that is present in the respiratory tract of dogs with canine infectious respiratory disease and which has a low level of homology to the enteric canine coronavirus, but which has a high level of homology to all bovine coronavirus strains (eg Quebec and LY138) and human coronavirus strain OC43. The CRCV spike, polymerase and hemagglutinin/esterase cDNA and protein partial sequences are listed in FIGS. (1) to (4), (13) and (14).

Abstract: Compositions and methods useful to enhance the development of the immune system of a growing animal are disclosed.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a cancer cell. Delivery of the cargo compound is accomplished by the use of protein transduction domains derived from cupredoxins. The invention further discloses methods for treating cancer and diagnosing cancer.

Abstract: The present invention provides for a novel oil-in-water (O/W) emulsion, with increased stability in the presence of bacterial or viral suspensions, especially those concentrated and non-purified or weakly purified. The emulsion of the present invention can act as vehicle for the delivery of a pharmaceutical composition comprising at least one immunogen and, in particular, an immunogen selected from the group comprising an inactivated pathogen, an attenuated pathogen, a subunit, a recombinant expression vector, and a plasmid or combinations thereof.

Abstract: This invention relates to a method of treating a dog for canine diseases comprising administering to the dog therapeutically effective amounts of a vaccine, wherein the vaccine comprises viral antigens, a bacterin, or both, and wherein the vaccine is administered subcutaneously or orally according to the schedules provided herein.

Abstract: This invention is based on the experimental finding that activators of Rho GTPases, namely the cytotoxic necrotizing factor 1 (CNF1), and DNT bear immunostimulatory properties towards the systemic response to orally administered ovalbumine. This invention concerns a vaccine composition including an immunoadjuvant compound, wherein the immunoadjuvant compound consists of a Rho GTPase activator.

Abstract: The present invention provides materials and methods to facilitate the pulmonary delivery of therapeutic agents. In some embodiments, agonists of tight junctions (e.g., zonulin agonists) are used in compositions to facilitate the uptake of therapeutic agents from the pulmonary mucosa.

Abstract: The present invention relates to compositions comprising cupredoxins, and their use to inhibit angiogenesis in mammalian cells, tissues, and animals, and particularly the angiogenesis that accompanies tumor development and particularly in humans. Specifically, the present invention relates to compositions comprising the cupredoxin(s), and or peptides that are variants, derivatives or structural equivalents of cupredoxins, which retain the ability to inhibit angiogenesis in mammalian cells, tissues or animals. These compositions may be peptides or pharmaceutical compositions, among others. The compositions of the invention may be used to treat any pathological condition that has as a symptom or cause, inappropriate angiogenesis, and particularly inappropriate angiogenesis related to tumor development.

Abstract: An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.

Abstract: Improved, low cost vaccines for administration to living subjects such as mammals and birds are provided, which include killed recombinantly modified microorganisms (whole cell recombinant bacterin vaccine), the latter including recombinant DNA encoding at least one protective protein (e.g., an antigenic protein) which has been expressed by the microorganisms prior to killing thereof. The protective protein(s) are operable to prevent or reduce the severity of a disease of the subject. The vaccine preparations of the invention do not require separation of the protective protein(s) from the host recombinant microorganism(s), thereby materially decreasing the complexity and cost of the vaccine formulations. A preferred vaccine against kennel cough includes recombinantly modified microorganisms which express protective antigens containing pertactin and filamentous hemagglutinin protein products.

Abstract: An acellular vaccine is provided which in use provides protection against Bordetella pertussis infections. The vaccine is based on the synergistic combination of two antigenes from B. pertussis, the 69 kDa, and the filamentous haemagglutinin antigens.

Abstract: The present invention relates to adjuvant compositions which are suitable to be used in vaccines. In particular, the adjuvant compositions of the present invention comprises a saponin and an immunostimulatory oligonucleotide, optionally with a carrier. Also provided by the present invention are vaccines comprising the adjuvants of the present invention and an antigen. Further provided are methods of manufacture of the adjuvants and vaccines of the present invention and their use as medicaments. Methods of treating an individual susceptible to or suffering from a disease by the administration of the vaccines of the present invention are also provided.

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 present invention pertains to Bordetella bacteria having a double mutation, a first mutation in a gene of the Type III secretion system and a second mutation in a gene of the adenylate cyclase toxin (CyaA) locus of the bacteria so that the mutations result in no Type III secretion system, a non-functional Type III secretion system, no CyaA protein, or a non-functional CyaA protein or a combination thereof. The Bordetella bacteria double mutant is attenuated while maintaining the efficacy of the bacteria to elicit an immune response. The present invention also pertains to vaccine compositions and methods for treating and immunizing a mammal against a disease caused by infection of Bordetella bacteria or a disease caused by a pathogen.

Abstract: Embodiments of the present invention generally comprise stabilizers for biological products that are free from animal origin excipients/components, such stabilizers functioning well in lyophilization procedures.

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 present invention relates to nanoparticle vaccines comprised of a carrier, particularly polymerized lipids, having multiple copies of an antigen or combinations of different antigens displayed on the carrier. Such antigen-displaying nanoparticles may also display a targeting molecule on its surface in order to direct it to a specific site or cell type to optimize a desired immune response. The present invention also relates to encapsulating an antigen or combinations of different antigens within such nanoparticles, with or without a targeting molecule displayed on its surface. The antigens used in this invention are effective to produce an immune response against a variety of pathological conditions.

Abstract: The invention relates to a method of 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: This invention relates to an immunogenic composition comprising a bacterial extract containing at least one expression products of the vrg genes of a strain of Bordetella chosen from B. pertussis, B. parapertussis, or B. bronchiseptica. The invention also relates to a method for producing the extract, comprising culturing the bacteria on blood medium to obtain isolated nonhemolytic colonies; inoculating cells of one or more colonies in liquid medium to give a suspension of cells; separating the cells from the liquid medium after culture; suspending the separated cells in a buffer comprising urea for at least an amount of time sufficient to form a bacterial lysate; and separating intact cells and insoluble material from soluble material, wherein the extract comprises the soluble material.

Abstract: A method of inducing either a TH1 polarized immune response, a TH2 polarized immune response or a combined TH1 and TH2 response to an antigen and associated vaccine formulations are disclosed. A method is provided for inducing a polarized TH1 response by parenteral administration of microparticles sized such that at least 50% of the microparticles are less than 5 ?m. The microparticles containing antigen entrapped or encapsulated by a biodegradable polymer. Additionally, a method is provided for inducing a polarized TH2 response by parenteral administration of nanoparticles sized such that at least 50% of the nanoparticles are less than 600 nm, the nanoparticles containing antigen entrapped or encapsulated by a biodegradable polymer. Vaccine formulations containing the B. pertussis antigens PTd, FHA or a combination of PTd and FHA are provided.

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: The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent induces of a range of immune responses.

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: This invention provides a composition of at least one Bordetella antigen and an effective adjuvant amount of interleukin-12 (IL-12), and uses thereof as a vaccine against Bordetella infection. Methods for using IL-12 as an adjuvant in combination with vaccines against Bordetella are also provided.

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: 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: This invention relates to vaccines and methods for protecting dogs against disease caused by Bordetella bronchiseptica. This invention also relates to combination vaccines and methods for protecting dogs against disease or disorder caused by canine pathogens, for example, infectious tracheobronchitis caused by Bordetella bronchiseptica, canine distemper caused by canine distemper (CD) virus, infectious canine hepatitis (ICH) caused by canine adenovirus type 1 (CAV-1), respiratory disease caused by canine adenovirus type 2 (CAV-2), canine parainfluenza caused by canine parainfluenza (CPI) virus, enteritis caused by canine coronavirus (CCV) and canine parvovirus (CPV), and leptospirosis caused by Leptospira Bratislava, Leptospira canicola, Leptospira grippotyphosa, Leptospira icterohaemorrhagiae or Leptospira pomona. The vaccines of the present invention include a Bordetella bronchiseptica p68 antigen.

Abstract: The invention relates to a method for making an inactivated vaccine of Mycoplasma hyopneumoniae by inactivating the bacteria with Thimerosal. The resulting bacterin is mixed with an adjuvant of aluminum hydroxide and DEAE dextran and injected into pigs. The resulting bacterin and adjuvant mixture can also be mixed with other bacteria such as Bordetella and Pasteurella, for further adjuvant effect. Protective immunity against mycoplasmal pneumonia is elicited in swine using these vaccines.