Abstract: Disclosed herein are novel nucleic acid and protein sequences that are essential to fertility. In particular, human Mater cDNA and protein sequences are provided. Functional MATER is required for female fertility; zygotes that arise from Mater null oocytes do not progress beyond the two-cell stage. Methods are described for detecting an autoimmune response to MATER in a subject by detecting autoantibodies that recognize an epitope of a MATER protein. Also provided are methods for diagnosis of infertility or reduced fertility by detecting presence of MATER protein autoantibodies in a subject. The disclosure also describes kits for detecting MATER autoantibodies comprising MATER protein.

Abstract: Protein sequences encoding antigenized antibodies for treatment of foot-and-mouth disease (FMD) or foot-and-mouth disease virus (FMDV) of swine is provided. The antigenized antibodies are created from the grafting of peptide epitopes derived from FMDV into swine antibody CDR loops. FMDV peptide epitopes are cloned by PCR from VP1 gene of FMDV. The overlapping PCR method is used to insert the FMDV peptide epitopes into the CDR regions of swine immnuoglobulin heavy and light chains genes. The resulting antigenized antibody genes were cloned into mammalian expression vector. The plasmids are transfected into CHO or myeloma cells. The stable transfectant cell line was selected for high yield of the desired protein antibodies.

Abstract: The invention provides methods and materials for treating inflammatory conditions. Specifically, the invention provides polypeptides, isolated nucleic acids, host cells, and methods that can be used to induce an antibody response in a mammal against an antigen such as C5 or C5a. For example, the methods and materials described herein can be used to reduce the effects of C5a within a mammal by reducing the amount of total and receptor bound C5a in the mammal.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: The invention concerns nucleic acid molecules derived from novel hepatitis D virus strains or isolates constituting genotypes different from known I, II and III genotypes, their fragments, corresponding proteins and their uses as diagnostic reagents. The invention also concerns a method for sensitive diagnosis of the hepatitis D virus (or delta hepatitis virus) and a method for epidemiologic monitoring of HDV-related infections.

Abstract: The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISATX247, and derivatives thereof. Mixtures of ISATX247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISATX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. The ratio of isomers in a mixture may range from about 10 to 90 percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the (Z)-isomer, based on the total weight of the mixture.

Abstract: A method for enhancing or inducing an immune response to WT1 is disclosed. In particular, the method comprises administering to a patient an immunogenic composition comprising an isolated polypeptide consisting of amino acids 1-249 of WT1 and a non-specific immune response enhancer.

Abstract: The invention relates to a method for quickly and effectively isolating and purifying five, namely the group 1, 2, 3, 10 and 13 allergens from grass pollen. The purification of said grass pollen is based on the inventive combination of hydrophobic interaction chromatography, gel filtration and cation exchange chromatography. The proteins obtained by the inventive method facilitate an improved diagnosis of pollen allergies and are used in pharmaceutical preparations for the therapy of pollenogenic diseases.

Abstract: Compositions and methods for the therapy of malignant diseases, such as leukemia and cancer, are disclosed. The compositions comprise one or more of a WT1 polynucleotide, a WT1 polypeptide, an antigen-presenting cell presenting a WT1 polypeptide, an antibody that specifically binds to a WT1 polypeptide; or a T cell that specifically reacts with a WT1 polypeptide. Such compositions may be used, for example, for the prevention and treatment of metastatic diseases.

Abstract: The present invention provides heteropolymer compositions and peptide compositions, and methods of making and using therapeutic compositions comprising amino acid heteropolymers for treatment of a subject for an autoimmune or an inflammatory disease, the heteropolymer compositions made by solid state synthesis. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.

Abstract: Compositions and methods for making and using therapeutic formulations of multivalent hybrid polypeptides comprising immunogenic peptides of M proteins from various different serotypes of group A streptococci and antibodies thereto are provided. Also provided are nucleic acids encoding such hybrid polypeptides. The hybrid polypeptide formulations may be used, for example, in methods for treating or preventing a microbial infection and eliciting a protective immune response having broadly protective opsonic antibodies in the absence of tissue cross-reactive antibodies.

Abstract: Novel vaccines for use against ?-hemolytic Streptococcus colonization or infection are disclosed. The vaccines contain an immunogenic amount of a variant of streptococcal C5a peptidase (SCP). Also disclosed is a method of protecting a susceptible mammal against ?-hemolytic Streptococcus colonization or infection by administering such a vaccine. Enzymatically inactive SCP, and polynucleotides encoding these SCP proteins are further disclosed.

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: The present invention provides peptides having T cell stimulating activity termed recombitope peptides. Recombitope peptides of the invention preferably comprise at least two T cell epitopes derived from the same or from different protein antigens, and more preferably comprise at least two regions, each region preferably having human T cell stimulating activity and each region comprising at least one T cell epitope derived from a protein antigen. Recombitope peptides of the invention can be derived from protein allergens, autoantigens, or other protein antigens. The invention also provides methods of diagnosing sensitivity to a protein allergen or other protein antigen in an individual, methods to treat such sensitivity and therapeutic compositions comprising one or more recombitope peptides. The invention further provides methods for designing recombitope peptides of the invention where the protein antigen to which the individual is sensitive has unknown or ill-defined T cell epitopes.

Abstract: The present invention relates to soluble P. gingivalis polypeptides derived from PG32 and PG33 and to polynucleotides encoding these polypeptides. The P. gingivalis polypeptides and nucleotides can be used in compositions for use in raising an immune response in a subject against P. gingivalis and treating or preventing or reducing the severity of the condition known as periodontitis or in other conditions related to infection with P. gingivalis.

Abstract: The invention provides methods for identifying peptide epitopes that activate CD4+ T cells involved in the pathogenesis of diseases, e.g., autoimmune diseases, susceptibility to which is determined by expression of particular class II MHC genes. The invention includes peptides derived from the IA-2 polypeptide by such a method, altered peptide ligands, and methods of therapy involving the use of altered peptide ligands.

Abstract: The invention provides isolated HLA DRB1*15-binding peptides consisting of the amino acid sequence set forth as SEQ ID NO:7 with 0–10 amino acids added to either or both ends of the amino acid sequence set forth as SEQ ID NO:7, and an endosomal targeting signal comprising an endosomal targeting portion of human invariant chain Ii or LAMP-1.

Abstract: Compositions and methods for the therapy of malignant diseases, such as leukemia and cancer, are disclosed. The compositions comprise one or more of a WT1 polynucleotide, a WT1 polypeptide, an antigen-presenting cell presenting a WT1 polypeptide, an antibody that specifically binds to a WT1 polypeptide; or a T cell that specifically reacts with a WT1 polypeptide. Such compositions may be used, for example, for the prevention and treatment of metastatic diseases.

Abstract: The present invention relates to the expression of peptides on viral particles, and more particularly to the expression of peptides on the interior or the viral capsid. Methods are described for modifying viruses so that exogenous epitopes are expressed on the interior of the viral capsid. Viruses that can be modified include (+) stranded RNA viruses, especially plant (+) stranded RNA viruses such as the cowpea mosaic virus. Internal expression is especially useful for the expression of hydrophobic epitopes. The modified viral particles also find use as vaccines and as such are capable of eliciting an immune response.

Abstract: Outer-membrane vesicles, Class 1 outer membrane proteins of Neisseria meningitidis, fragments or oligopeptides containing epitopes of the Class I OMP can be used to immunize against meningococcal disease.

Abstract: The present invention provides glucan-based compositions and methods for stimulating an immune response against mutans streptococci components and vaccines and methods for the treatment and prevention of dental caries. In a preferred embodiment, a glucan polymer, preferably WSG, is covalently bound to one or more T cell-dependent antigens to form a conjugate vaccine. The T cell-dependent antigen preferably contains epitopes of one or more mutans streptococcal proteins, such as a glucosyltransferase. Moreover, one or more moieties, including haptens, may be conjugated to the glucan-T cell-dependent composition. In a preferred embodiment, these moieties are peptides which contain immunogenic epitopes corresponding to components of a mutans streptococcus.

Abstract: Immunogenic polypeptides comprising hepatitis C virus (HCV) immunogens are described. The HCV immunogen comprises the amino acid sequence Xaa-Thr-Xaa-Val-Thr-Gly-Gly-Xaa-Ala-Ala-Arg-Thr-Thr-Xaa-Gly-Xaa-Xaa-Ser-Leu-P he-Xaa-Xaa-Gly-Xaa-Ser-Gln-Xaa-Ile-Gln-Leu-Ile (SEQ ID NO:8). The immunogenic polypeptide can be coupled to a bacterial toxoid, such as a diphtheria toxoid.

Abstract: The present invention provides a vaccine for inducing an immune response in mammal to a specific antigen, where the vaccine comprises a unit dose of a binary toxin protective antigen and the antigen, which is bound to a binary toxin protective antigen binding protein. In one embodiment the vaccine is comprised of an anthrax protective antigen and the antigen bound to anthrax protective antigen binding protein. The present invention also provides a method of immunizing a mammal against an antigen using the vaccine, and a method of inducing antigen-presenting mammalian cells to present specific antigens via the MHC class I processing pathway.

Abstract: Recombinant hybrid streptococcal M protein antigens are provided which elicit protective antibodies against Group A streptococci and prevent rheumatic fever. Recombinant hybrid genes which encode the antigen are provided. Vaccine compositions and methods of administering the compositions are provided to elicit immunity against Group A streptococci.

Abstract: An isolated antigen against a Mycoplasma, prepared by a method including providing a sample of a Mycoplasma and an antibody probe, probing the Mycoplasma sample with the antibody probe to detect at least one antigen, and isolating the antigen detected. The antibody probe includes at least one antibody against the Mycoplasma that is produced by a method including (a) providing a biological sample taken a short time after an immune animal has been challenged with a Mycoplasma or Mycoplasma extract taken from the infection site or an area of a lesion or an area close to the infection site or lesion; (b) isolating cells from the biological sample; (c) culturing the cells in vitro in a suitable culture medium; and (d) harvesting antibodies produced from the cell.

Abstract: A Candida albicans bloodstream infections cause significant morbidity and mortality in hospitalized patients. Filament formation and adherence to host cells are critical virulence factors of C. albicans. Multiple filamentation regulatory pathways have been discovered, however the downstream effectors of these regulatory pathways remain unknown. The cell surface protein, Als1p, is a downstream effector of the filamentation regulatory pathway and is regulated by Efg1p. Als1p mediates adherence to endothelial cells in vitro and is required for virulence. The blocking of adherence by the organism is described resulting from the use of a composition and method disclosed herein. Specifically, a pharmaceutical composition comprised of a gene product from the ALS1 gene family is administered as a vaccine to generate an immune response capable of blocking adherence of the organism.

Abstract: We isolated and characterized a new surface mutant of the hepatitis B virus surface antigen (HBsAg). The mutant was isolated from a symptomatic patient with Down's syndrome who was found to be persistently positive for both for HBsAg and anti-HBs Antibody (Ab) with an equally long-lasting anti-HB core (c) IgM Ab.

Abstract: A vaccine, effective in inducing the production of antibodies with which to immunize a second subject passively against infection by Gram-negative bacteria and LPS-mediated pathology, comprises a non-covalent polyvalent complex formed between purified, detoxified LPS derived from E. coli and purified outer membrane protein derived from N. meningitidis. The same vaccine will also actively immunize a host subject against Gram-negative bacterial infections and LPS-mediated pathology. Meningococcal infections are included among those Gram-negative bacterial infections protected against by the vaccine.

Abstract: The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISATX247, and derivatives thereof. Mixtures of ISATX247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISATX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. The ratio of isomers in a mixture may range from about 10 to 90 percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the (Z)-isomer, based on the total weight of the mixture.

Abstract: The present invention features a Bacillus anthracis lethal factor substrate. The substrate can be used for example to measure lethal factor activity. Preferred substrates contain one or mare detectable labels and have a sufficiently high turnover rate for applications in a high throughput screen.

Abstract: A method for judging an autoimmune disease by detecting the existence of an anti-Reg protein autoantibody in a specimen; and a method for judging insulin-dependent or non-insulin-dependent diabetes mellitus. A method for detecting an anti-Reg protein autoantibody by bringing into a specimen into contact with an antigen component and detecting the formation of an immune complex. A reagent for diagnosing autoimmune disease which contain an antigen component capable of binding specifically to the anti-Reg protein autoantibody; and a reagent for diagnosing insulin-dependent or non-insulin-dependent diabetes mellitus.

Abstract: The present invention relates to a composition comprsing a peptide immunogen useful for the prevention and treatment of Alzheimer's Disease. More particularly, the peptide immunogen comprises a main functional/regulatory site, an N-terminal fragment of Amyloid ? (A?) peptide linked to a helper T cell epitope (Th) having multiple class II MHC binding motifs. The peptide immunogen elicit a site-directed immune response against the main functional/regulatory site of the A? peptide and generate antibodies, which are highly cross-reactive to the soluble A?1-42 peptide and the amyloid plaques formed in the brain of Alzheimer's Disease patients. The antibodies elicited being cross reactive to the soluble A?1-42 peptide, promote fibril disaggregation and inhibit fibrillar aggregation leading to immunoneutralization of the “soluble A?-derived toxins”; and being cross-reactive to the amyloid plaques, accelerate the clearance of these plaques from the brain.

Abstract: The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from Streptococcus pneumoniae. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising unique fragment of at least 10 nucleotides of the 37-kDa protein. Additionally, multiple antigenic peptides that provide protection against S. pneumoniae challenge are provided. These multiple antigen peptides comprise the peptides that immunospecifically bind to the monoclonal antibodies. Also provided are vaccines comprising such immunogenic peptides, and methods of conferring protective immunity against Streptococcus pneumoniae infection by administering therapeutic composition comprising the immunogenic peptides of the invention.

Abstract: Newly elucidated sequences of hepatitis C virus type 4 and type 5 are described, together with those of a newly discovered type 6. Unique type-specific sequences in the NS4, NS5 and core regions enable HCV detection and genotyping into types 1 to 6. Antigenic peptides and immunoassays are described.

Abstract: The invention relates to polyepitope carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are use useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines arm particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: The production of a purified extracellular bacterial signal called autoinducer-2 is regulated by changes in environmental conditions associated with a shift from a free-living existence to a colonizing or pathogenic existence in a host organism. Autoinducer-2 stimulates LuxQ luminescence genes, and is believed also to stimulate a variety of pathogenesis related genes in the bacterial species that produce it. A new class of bacterial genes is involved in the biosynthesis of autoinducer-2.

Abstract: The invention relates to an adjuvant product which is intended to improve the activity of a molecule when administered to a host, characterized in that it comprises at least one part of the P40 protein of Klebsiella pneumoniae or a protein having at least 80% homology with the P40 protein of Klebsiella pneumoniae. The invention also relates to nucleotide sequences which encode these peptides or proteins and to the use of these sequences as a medicament. More particularly, such DNA sequences can be used in compositions which are intended for immunization by the intramuscular or intradermal route.

Abstract: The invention is directed to a peptide, comprising the amino acid sequence substantially as denoted by SEQ ID NO:1 and biologically functional homologues and derivatives thereof.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as breast cancer, are disclosed. Compositions may comprise one or more breast tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a breast tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as breast cancer. Diagnostic methods based on detecting a breast tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Abstract: A purified preparation of a peptide consisting essentially of an amino acid sequence identical to that of a segment of a naturally-occurring human protein, said segment being of 10 to 30 residues in length, inclusive, wherein said peptide binds to a human major histocompatibility complex (MHC) class II allotype.

Abstract: The present invention relates to a polypeptide of about 8 to about 100 amino acids comprising or consisting of at least 8 contiguous amino acids selected from the core, and/or the NS3 regions of the HCV polyprotein, with said contiguous amino acids containing a T-cell stimulating epitope.

Abstract: The present invention provides methods and compositions for eliciting protective immunity against malaria. In particular, the invention relates to universal T-cell epitopes that elicit T-cell responses in individuals of differing genetic backgrounds. Immunogenic compositions and vaccines including malaria-specific universal T-cell epitopes are disclosed.

Abstract: Compositions and methods for the detection and therapy of breast cancer are disclosed. The compounds provided include nucleotide sequences that are preferentially expressed in breast tumor tissue, as well as polypeptides encoded by such nucleotide sequences. Vaccines and pharmaceutical compositions comprising such compounds are also provided and may be used, for example, for the prevention and treatment of breast cancer. The polypeptides may also be used for the production of antibodies, which are useful for diagnosing and monitoring the progression of breast cancer in a patient.

Abstract: The invention provides fibroblast growth factor homologous factor (FHF) polypeptides and nucleic acid molecules that encode them. Also included in the invention are diagnostic and therapeutic methods using FHF polypeptides and nucleic acids.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: The use of cognate heat shock protein 70-peptide complex to elicit an immune response against cancer and viral, bacterial and other infectious agents.

Abstract: The present invention provides a vaccine for inducing an immune response in mammal to a specific antigen, where the vaccine comprises a unit dose of a binary, cytotoxic T lymphocyte vaccine comprising an anthrax protective antigen and a full length protein antigen bound to a nontoxic anthrax protective antigen binding protein comprising at least about the first 250 amino acid residues of the lethal factor of Bacillus anthracis and less than all of the amino acid residues of the lethal factor. The present invention also provides a method of immunizing a mammal against an antigen using the vaccine, and a method of inducing antigen-presenting mammalian cells to present specific antigens via the MHC class I processing pathway.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as breast cancer, are disclosed. Compositions may comprise one or more breast tumor proteins, immunogenic portion thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a breast tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as breast cancer. Diagnostic methods based on detecting a breast tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Abstract: This invention relates to human immunodeficiency virus (HIV) protein fragments which have antiviral activity, and particularly relates to HIV peptides derived from the HIV transmembrane glycoprotein (gp41) which inhibit HIV-induced cell-cell fusion. This invention further relates to methods for the inhibition of enveloped viral infection, and to methods that modulate biochemical processes which involve coiled coil peptide interactions.

Abstract: The present invention provides a fusion polypeptide comprising a chemokine and either a tumor or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing HIV infection.