Abstract: A novel dosing regimen for the administration of botulinum toxin based on the pattern, quantity, and location of neuromuscular junctions in the target tissue. Because the number of neuromuscular junctions in a target tissue remains generally stable throughout life and because the pharmacological effect of botulinum toxin is localized at the neuromuscular junction, dosing efficacy is unaffected by muscle mass, age of the patient, or body weight.

Abstract: The subject of the invention is a method for adjuvanting LPS of a Gram-negative bacterium, according to which LPS or LPS liposomes (LPS formulated in liposomes) is (are) mixed with the lipidated human-transferrin receptor subunit B (TbpB protein) of Neisseria meningitidis or a lipidated fragment thereof; or (ii) LPS and the lipidated TbpB of N. meningitidis or a lipidated fragment thereof are formulated together in liposomes; or (iii) LPS is conjugated with the lipidated TbpB of N. meningitidis or a lipidated fragment thereof; in order to obtain a preparation which does not contain OMVs and which is capable of inducing, after administration to a mammal, an anti-LPS immune response which is improved by comparison with the anti-LPS immune response observed after administration of the corresponding preparation in which the lipidated TbpB of N. meningitidis or a lipidated fragment thereof is omitted; as well as vaccine compositions thereof.

Abstract: The invention relates to, in part, secreted proteins of bacterial pathogens and methods for their use. More specifically, the invention provides in part several new common secreted proteins for A/E pathogens. In some embodiments of the invention, these polypeptides and nucleic acid molecules encoding these polypeptides, or portions thereof, are useful as vaccines, diagnostics, or drug screening tools for A/E pathogenic infections, or as reagents.

Abstract: The present invention provides vaccine and pharmaceutical compositions for treating or preventing bacterial inventions. The vaccine compositions of the invention include a carbapenemase such as a serine carbapenemase, a metallo-?-lactamase or an immunogenic fragment thereof. The pharmaceutical compositions include an anti-carbapenemase antibody or fragment thereof. Also provided are methods for treating and preventing a bacterial infection using the vaccine and pharmaceutical compositions of the invention. The invention further provides antibody conjugates that include an antibody or fragment thereof conjugated to a siderophore or an analog thereof.

Abstract: The invention provides a composition for use in raising an immune response to P. gingivalis in a subject, the composition comprising an amount effective to raise an immune response of at least one polypeptide having an amino acid sequence substantially identical to at least 50 amino acids, or an antigenic or immunogenic portion, of one of the polypeptides corresponding to accession numbers selected from the group consisting of AAQ65462, AAQ65742, AAQ66991, AAQ65561, AAQ66831, AAQ66797, AAQ66469, AAQ66587, AAQ66654, AAQ66977, AAQ65797, AAQ65867, AAQ65868, AAQ65416, AAQ65449, AAQ66051, AAQ66377, AAQ66444, AAQ66538, AAQ67117 and AAQ67118. The invention also provides a method of preventing or treating a subject for P. gingivalis infection comprising administering to the subject a composition of the invention.

Abstract: There is provided a vaccine for controlling Clostridium perfringens in animals, and particularly necrotic enteritis in poultry. The vaccine may comprise a C. perfringens antigenic polypeptide or variant thereof, a nucleic acid encoding the C. perfringens antigenic polypeptide or variant thereof, or a recombinant cell producing the C. perfringens antigenic polypeptide or variant thereof.

Abstract: This invention relates to the use of a composition comprising a polysaccharide and a botulinum toxin for reducing a skin wrinkle. In some embodiments, the polysaccharide comprises disaccharides. In some embodiments, the average molecular weight of a disaccharide unit of the polysaccharide is between about 345 D and about 1,000 D.

Abstract: Biodegradable neurotoxin implants and methods of making and using such implants are provided. Biodegradable neurotoxin implants include a neurotoxin, a biodegradable polymer component, and an acidity regulating component. The biodegradable polymer component is effective in controlling the release of the neurotoxin from the implant when the implant is located in a patient's body. The acidity regulating component is effective in maintaining a pH of the implant in a desired range that may be effective in stabilizing the neurotoxin as the implant biodegrades when the implant is located in a patient's body. In one embodiment, an implant includes a botulinum toxin, a biodegradable polymer, and either monomers from which a biodegradable polymer is derived or oligomers including monomeric units substantially identical to a monomer from which a biodegradable polymer is derived, or a combination of such monomers and oligomers. The oligomers and biodegradable polymer may be derived from a single type of monomer.

Abstract: This invention provides a method for stimulating in an individual an immune response against M. catarrhalis. The method comprises administering to an individual a composition comprising M. catarrhalis OppA protein in an amount effective to stimulate an immune response against M. catarrhalis in the individual.

Abstract: Microparticles with adsorbent surfaces, methods of making such microparticles, and uses thereof, are disclosed. The microparticles comprise a polymer, such as a poly(?-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and the like, and are formed using cationic, anionic, or nonionic detergents. The surface of the microparticles efficiently adsorb biologically active macromolecules, such as DNA, polypeptides, antigens, and adjuvants. Also provided are compositions of an oil droplet emulsion having a metabolizable oil and an emulsifying agent. Immunogenic compositions having an immunostimulating amount of an antigenic substance, and an immunostimulating amount of an adjuvant composition are also provided.

Abstract: The present invention includes a composition including as one component a slurry matrix that is a liquid at room temperature and a gel at physiological pH, physiological salt concentrations and/or physiological temperatures and as a second component one or more antigens. Also include are methods of inducing an immune response in a subject and vaccinating a subject by administering such compositions.

Abstract: Nucleic acid immunisation is achieved by delivering a self-replicating RNA encapsulated within a small particle. The RNA encodes an immunogen of interest, and the particle may deliver this RNA by mimicking the delivery function of a natural RNA virus. Thus the invention provides a non-virion particle for in vivo delivery of RNA to a vertebrate cell, wherein the particle comprises a delivery material encapsulating a self-replicating RNA molecule which encodes an immunogen. These particles are useful as components in pharmaceutical compositions for immunising subjects against various diseases.

Abstract: The disclosure provides compositions that include microparticles or nanoparticles of beta inulin or inulin acetate and an active agent, where the active agent is contained within individual microparticles or nanoparticles. The active agent can be, for example, a vaccinating antigen, an antigenic peptide sequence, or an immunoglobulin. The compositions can be incorporated into various formulations for administration to a subject such as a human or animal. The invention further provides methods of using the compositions and formulations, including methods of stimulating an immune response in a subject, or enhancing an immune response in a subject, for the purpose of treating, preventing, or inhibiting an infectious disease, autoimmune disease, immunodeficiency disorder, neoplastic disease, degenerative disease, an aging disease, or a combination thereof.

Abstract: The invention provides non-replicating compositions, and methods for the delivery of these compositions containing pharmaceuticals, biologically relevant molecules, and/or antigens to the host, by administration via a mucosal route such as the intranasal. This invention provides non-replicating vaccine compositions and methods for the delivery of antigens in these vaccine compositions comprising an antigen and a self-adjuvanting carrier, useful for inducing antigen-specific mucosal and systemic immune responses in the host upon immunization via a mucosal route such as intranasal. The vaccine compositions comprise multivalent cations in association with a plurality of spherical archaeal polar lipid aggregates containing aqueous compartments, the AMVAD structure, formed by the interaction of archaeosomes and antigen(s) with multivalent cations such as Ca2+, wherein the AMVAD structure acts as a self-adjuvanting carrier for the antigen(s) in the vaccine composition.

Abstract: Vaccines for conferring immunity in mammals to infective pathogens are provided, as well as vectors and methods for plastid transformation of plants to produce protective antigens and vaccines for oral delivery. The invention further provides transformed plastids having the ability to survive selection in both the light and the dark, at different developmental stages by using genes coding for two different enzymes capable of detoxifying the same selectable marker, driven by regulatory signals that are functional in proplastids as well as in mature chloroplasts. The invention utilizes antibiotic-free selectable markers to provide edible vaccines for conferring immunity to a mammal against Bacillus anthracis, as well as Yersina pestis. The vaccines are operative by parenteral administration as well. The invention also extends to the transformed plants, plant parts, and seeds and progeny thereof. The invention is applicable to monocot and dicot plants.

Abstract: RNA is encapsulated within a liposome for in vivo delivery. The RNA encodes a polypeptide of interest, such as an immunogen for immunisation purposes. The liposome includes at least one compound selected from the group consisting of compounds of formula (I) and formula (XI).

Abstract: The present invention relates to a modified polypeptide with a biological activity to lyse cell walls of bacteria, wherein the polypeptide has no caspase, clostripain, enterokinase, factor Xa, granzyme B, staphylococcus peptidase I (V8 Protease), plasmin, streptopain, bacillolysin and/or thrombin cleavage site. The invention further relates to nucleic acids with a sequence encoding a polypeptide according to the present invention.

Abstract: Various specific meningococcal proteins are disclosed. The invention provides related polypeptides, nucleic acids, antibodies and methods. These can all be used in medicine for treating or preventing disease and/or infection caused by meningococcus, such as bacterial meningitis.

Abstract: The present invention discloses a method for inhibiting the growth of Mycobacterium tuberculosis, comprising: administering at least one selective binding agent such as an anti-CD13 antibody or a CD13 antagonist which can bind a CD13 receptor of a cell to inhibit infection of Mycobacterium tuberculosis. Administration of anti-CD13 antibody can reduce an expression level of the CD13 receptor, inhibit entry of Mycobacterium tuberculosis into monocytes, reduce survival of Mycobacterium tuberculosis in monocytes, and kill Mycobacterium tuberculosis effectively.

Abstract: Described is an immunostimulatory oligodeoxynucleic acid molecule (ODN) having the structure according to formula (I), wherein any NMP is a 2? deoxynucleoside monophosphate or monothiophosphate, selected from the group consisting of deoxyadenosine-, deoxyguanosine-, deoxyinosine-, deoxycytosine-, deoxyuridine-, deoxythymidine-, 2-methyl-deoxyinosine-, 5-methyl-deoxycytosine-, deoxypseudouridine-, deoxyribosepurine-, 2-amino-deoxyribosepurine-, -6-S-deoxyguanine-, 2-dimethyl-deoxyguanosine- or N-isopentenyl-deoxyadenosine-monophosphate or -monothiophosphate, NUC is a 2? deoxynucleoside, selected from the group consisting of deoxyadenosine-, deoxyguanosine-, deoxyinosine-, deoxycytosine-, deoxyuridine-, deoxythymidine-, 2-methyl-deoxyinosine-, 5-methyl-deoxycytosine-, deoxypseudouridine-, deoxyribosepurine-, 2-amino-deoxyribosepurine-, 6-S-deoxyguanine-, 2-dimethyl-deoxyguanosine- or N-isopentenyl-deoxyadenosine, any X is O or S, a and b are integers from 0 to 100 with the proviso that a+b is between 4 and 150,

Abstract: The present invention provides compositions and methods for generating and cryopreserving dendritic cells with superior functionality in producing stronger signals to T cells, resulting in a more potent DC-based anti-tumor vaccine. The present invention includes mature, antigen loaded DCs activated by Toll-like receptor agonists that induce clinically effective immune responses, preferably when used earlier in the disease process. The DCs of the present invention produce desirable levels of cytokines and chemokines, and further have the capacity to induce apoptosis of tumor cells. The cells can be cryopreserved and thawed for later use, thereby reducing the need for repeated pheresis and elutriation processes during vaccine production. These methods can also be utilized to directly target molecules involved in carcinogenetic signaling pathways and cancer stem cells.

Abstract: The present invention provides a method of classifying an epitope displayed by a polypeptide; a method of determining the presence of an epitope on a polypeptide encoded by a test nucleotide sequence; and a method of generating a nucleotide sequence encoding a polypeptide that exhibits a selected epitope. The present invention provides antigenic polypeptides that display selected epitope(s); chimeric macromolecules comprising such polypeptides; and compositions comprising the antigenic polypeptides or chimeric macromolecules. The present invention further provides methods of inducing an immune response to a Chlamydia. The present invention further provides arrays of nucleic acids, arrays of polypeptides, and arrays of antibodies, which arrays are useful in identification and/or classification of a Chlamydia.

Abstract: Methods are disclosed for treating or preventing graft versus host disease in a subject. The methods include selecting a subject in need of treatment for graft versus host disease; and administering to the subject a therapeutically effective amount of a TLR5 agonist such as a flagellin polypeptide, or a polynucleotide encoding the flagellin, thereby treating or preventing graft versus host disease in the subject. Methods are also disclosed for reducing susceptibility to an opportunistic infection in a subject who is a bone marrow transplant recipient. The methods include selecting a subject who has had a bone marrow or hematopoietic stem cell transplant; and administering to the subject a therapeutically effective amount of a TLR5 agonist such as a flagellin polypeptide or a polynucleotide encoding the polypeptide, and administering to the subject an effective amount antigen of the opportunistic infection, thereby reducing the susceptibility to the opportunistic infection in the subject.

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

Abstract: Whole-cell vaccines and methods for their use in producing protective immune responses in vertebrate hosts subsequently exposed to pathogenic bacteria. The present invention involves a method of enhancing antigen presentation by intracellular bacteria in a manner that improves vaccine efficacy. After identifying an enzyme that has an anti-apoptotic effect upon host cells infected by an intracellular microbe, the activity of the enzyme is reduced, thereby modifying the microbe so that it increases immunogenicity. Also, the present invention provides a method of incrementally modifying enzyme activity to produce incrementally attenuated mutants of the microbe from which an effective vaccine candidate can be selected.

Abstract: Compositions and methods comprising dendritic cells expressing elevated levels of fascin 1 useful in immunotherapy are disclosed.

Abstract: A pharmaceutical composition including an adjuvant effective amount of a protected inosine monophosphate (IMP) compound. The pharmaceutical composition includes the protected IMP compound alone, or in combination with vaccine agents with or without additional adjuvants. The pharmaceutical composition can be utilized as a vaccine composition or can be included with existing vaccine compositions in order to increase a specific T lymphocyte mediated immune response thereto. Various methods relating to the pharmaceutical composition and the vaccine are described herein. The vaccines can be employed to prevent or treat infections. Additionally, the pharmaceutical compositions not only increase T-cell responses, but also confer, by pretreatment, non-specific protection against a variety of pathogens. This combination of actions is appropriate for enhancing defense against bioterrorism with organisms like smallpox and anthrax.

Abstract: The present invention provides an immunogenic composition comprising one or more Streptococcus uberis sortase-anchored surface proteins, or an immunogenic part thereof, wherein the composition is capable of eliciting an immune response, when administered to a subject.

Abstract: The present invention provides improved vaccination methods for increased protection against ileitis. The methods provide for the vaccination of young animals, preferably piglets, between 10 and 26 days of age, vaccination of pregnant sows during the second or third stages of gestation, and a combination of these methods. Vaccination of the pregnant sows can occur using repeated and/or high doses of Lawsonai antigen prior to farrowing.

Abstract: The present invention is directed to a novel live attenuated isolate and sub-isolets thereof of a strain of the pathogen Edwardsiella ictaluri for protecting fish from ESC infection or disease, a vaccine composition comprising the isolet, a method of oral delivery of the vaccine and any vaccine, and an apparatus designed to effectively mix the vaccine with fish feed and deliver the vaccine to fish.

Abstract: This disclosure demonstrates a novel therapy immunological approach using polyamine-based therapy (PBT) for relieving tumor-induced suppression of the patient's immune system. The demonstration of the pharmacological release from the naturally occurring polyamine-mediated immune suppression offers profound impact on the immunotherapy of cancer together with a variety of diseases caused by the disease-causing vector's ability to evade an immune reaction. This therapeutic approach is equally applicable to disease states whereby immune system suppression by polyamines has been demonstrated including; bacterial infections, parasitic infections including malaria and typanosomiasis, viral infections, peptic ulcers and gastric cancer due to H. Pylori infection together with prevention of pregnancy. With a small molecule drug, used in combination with DFMO, the pharmacological manipulation of polyamine levels for therapeutic benefit in various disease states is possible.

Abstract: Polypeptides that can elicit antibodies that are bactericidal for different fHbp variant strains of N. meningitidis, and methods of use, are provided.

Abstract: The present invention is directed to methods of preventing reactivation of active and latent M. tuberculosis infections by administering a pharmaceutical composition comprising a nucleic acid encoding a Mtb72f fusion protein, or a Mtb72f fusion protein or an immunogenic fragment thereof, for example together with an adjuvant. The Mtb72f nucleic acid or fusion protein can be administered with one or more chemotherapeutic agents effective against a M. tuberculosis infection. The methods also provide for shortening the time course of a chemotherapeutic regimen against a M. tuberculosis infection.

Abstract: The present invention discloses new antigens of Mycobacterium avium subsp. paratuberculosis, antigenic compositions comprising at least two of said antigens, as well as epitopes, antibodies or hypervariable fragments thereof and nucleotide sequences coding for them. The present invention also concerns their use in diagnosis and/or vaccination against Mycobacterium avium subsp. paratuberculosis, in mammals, and in particular in cattle, but also in sheep and caprines. The invention also concerns their potential application in diagnosis and/or vaccination against Crohn's disease in human.

Abstract: It is disclosed herein that agents that affect the activity and/or expression of CXCL16 can be used to alter the uptake of D-type CpG oligodeoxynucleotides (D ODNs). Methods of inducing an immune response are disclosed that include administering agents that increase the activity and/or expression of CXCL16 and a D ODN. Methods of decreasing an immune response to a CpG ODN are also disclosed. These methods include administering an agent that decreases the activity and/or expression of CXCL16. Compositions including one or more D-type ODNs and an agent that modulates that activity and/or expression of CXCL16 are provided.

Abstract: The present invention provides a method of vaccinating a young animal against L. intracellularis infection comprising the step of administering to an animal an effective dose of L. intracellularis antigen. It also provides a method of vaccinating an animal, preferably a young animal, having anti-L. intracellularis antibodies or is exposed to anti-L. intracellularis antibodies. In particular, those anti-L.intracellularis antibodies are maternally derived antibodies.

Abstract: The present invention relates inter alia to the use of a combination of a vaccine against Lawsonia intracellularis and an anti-Lawsonia antibiotic for the prevention or reduction of early, preferably fulminant Lawsonia intracellularis infections. The present invention relates particularly to the use of a live Lawsonia intracellularis vaccine in conjunction with an antibiotic that is effective against Lawsonia intracellularis, for the avoidance or reduction of early Lawsonia intracellularis infections in animals.

Abstract: The invention provides proteins from Staphylococcus aureus including amino acid sequences and the corresponding nucleotide sequences. The proteins are useful for vaccines, immunogenic compositions, diagnostics, enzymatic studies and also as targets for antibiotics.

Abstract: Methods for synthesis and manufacture of polysaccharide-protein conjugate vaccines at high yield are provided. The methods involve reaction of a hydrazide group on one reactant with an aldehyde or cyanate ester group on the other reactant. The reaction proceeds rapidly with a high conjugation efficiency, such that a simplified purification process can be employed to separate the conjugate product from the unconjugated protein and polysaccharide and other small molecule by-products.

Abstract: The invention relates to a combination vaccine against Mycobacterium avium subspecies paratuberculosis (MAP) and M. tuberculosis and/or M. bovis for use in methods of immunizing a subject against mycobacterial infection, preventing or treating mycobacterial infection, and preventing a disease associated with mycobacterial infection.

Abstract: Broad-based, cross-protective, O-serotype independent vaccines against Shigella and related pathogenic organisms are provided. The vaccines comprise one or more of the type III secretion (TTS) apparatus needle proteins IpaD and IpaB, and/or the IpaB cognate chaperone protein IpgC. Chimeric proteins of IpaD and IpaB, and/or IpgC are also encompassed.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg.

Abstract: Novel polynucleotide and amino acids of Brachyspira hyodysenteriae are described. These sequences are useful for diagnosis of B. hyodysenteriae disease in animals and as a therapeutic treatment or prophylactic treatment of B. hyodysenteriae disease in animals. These sequences may also be useful for diagnostic and therapeutic and/or prophylactic treatment of diseases in animals caused by other Brachyspira species.

Abstract: The present invention relates, in general, to polypeptides having antigenic epitopes from granulocytic ehrlichia (GE) proteins and methods of use thereof.

Abstract: This invention relates to compositions and methods of preparing stable adjuvant diluent stock solutions and final adjuvant solutions comprising glycolipids, weak acids, alcohols, nonionic surfactants and buffers.

Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and an enhanced Clostridial toxin binding domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.

Abstract: The present invention relates to the use of a therapeutically effective amount of abscisic acid (ABA) or its analogs to treat or prevent inflammation induced by exposure to lipopolysaccharide (LPS) or respiratory inflammation. The invention also relates to methods and composition for enhancing vaccine efficacy using ABA.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: The present invention relates to methods for treating or preventing a disease or disorder in an animal caused by infection by Mycoplasma hyopneumoniae (M. hyo) by administering to the animal at approximately three (3) to ten (10) days of age, a single dose of an effective amount of a M. hyo vaccine. The M. hyo vaccine can be a whole or partial cell inactivated or modified live preparation, a subunit vaccine, or a nucleic acid or DNA vaccine. The M. hyo vaccine administered in accordance with the present invention can be synthesized or recombinantly produced.