Abstract: The invention is in general directed to methods and compositions for preventing or treating infections by viruses involved in persistent and/or latent infections. The methods and compositions are directed toward the prevention and treatment of infections caused by viruses such as, for example, herpesviruses, retroviruses, hepatitis viruses, and papillomaviruses, including, for example, cytomegalovirus.

Abstract: Described are a method for the identification of extracellular epitopes of Epstein Barr virus (EBV) encoded membrane proteins, expressed on the outer cell surface of EBV-transformed mammalian cells, methods for the selection and preparation of antibody reagents specific for the said epitopes, as well as peptides, including extracellular domains of Epstein Barr Virus encoded tumour cell associated membrane proteins, the use of said peptide for immunization and therapeutic vaccination to induce antibodies and T-cells reactive with said domains, the use of said antibody reagents for the production of targeting cells, tumour cell purging and as diagnostic for and medicament against EBV-mediated malignant cell growth.

Abstract: Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (?-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.

Abstract: The present invention relates to a pharmaceutical composition containing an mRNA that is stabilised by sequence modifications in the translated region and is optimised for the translation. The pharmaceutical composition according to the invention is particularly suitable as an inoculating agent as well as a therapeutic agent for tissue regeneration. In addition a process is described for determining sequence modifications that serve for the stabilisation and translation optimisation of mRNA.

Abstract: The present invention features a human antibody that specifically binds to human cytomegalovirus (HCMV), its encoding nucleic acid(s), and use of the antibody/nucleic acid(s) in treating HCMV infection.

Abstract: The invention provides an immunogenic composition comprising at least one antigen in association with micropar-tides, wherein the microparticles are in the same size range as viruses. In addition the invention also provides vaccine compositions and methods of eliciting immune responses in a subject.

Abstract: Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit human CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.

Abstract: The invention described herein relates to a method for identifying the antigenic regions of HCMV proteins involved in the human B-cell response to HCMV infection, for combining such antigenic regions in the form of chimeric fusion products, and their use as diagnostic and immunogenic agents.

Abstract: Disclosed herein are methods of modulation of the viability of a cell. Further disclosed herein are methods of modulating an immune response. Further disclosed herein are methods of identifying agents capable of modulation of the viability of a cell or an immune response. Further disclosed herein are agents and compositions capable of modulation of the viability of a cell or an immune response.

Abstract: Briefly described, virosomes, methods of preparing virosomes, immunogenic compositions that include virosomes, and methods of eliciting an immune response using immunogenic compositions that include virosomes are described herein. A virosome can include at least one viral surface envelope glycoprotein expressed on the surface of the virosome. The virosome can also optionally include at least one adjuvant molecule expressed on the surface of the virosome.

Abstract: Methods of eliciting humoral responses, methods of immunization, and methods of vaccination using lentiviral vector are disclosed. Additionally, immunogenic compositions and vaccines for West Nile Virus are disclosed.

Abstract: The present invention relates to an immuno-therapeutic and prophylactic vaccine comprising monocytes or immature myeloid cells (IMCs) loaded with the ligand of natural killer T cell and an antigen for the prevention and treatment of infectious disease or cancer, more precisely, an immuno-therapeutic and prophylactic vaccine comprising monocytes or IMCs loaded with ?-galactosylceramide (?GalCer), a kind of glycolipid and a natural killer T cell ligand, and antigen. Monocytes or immature myeloid cells (IMCs) therein, which are easily obtainable, unlike dendritic cells, not only induce a significant level of cytotoxic T lymphocyte responses but also have a prophylactic and therapeutic effect on malignant tumor. Therefore, the immuno-therapeutic and prophylactic vaccine of the present invention can be effectively used as an immunotherapeutic agent.

Abstract: A method of detecting osteoporosis in a mammalian is disclosed herein which includes: a) obtaining a sample of a bone related tissue or cells; and b) measuring the concentration of at least a marker which is either bacteria, bacteria produced factors, or HSPs. The method may further include comparing the concentration with concentrations from the same individual over a period of time or against a standard concentration. The marker may be a bacteria, a chaperone molecule, or a bacteria produced. Also provided herein is a method of treating or preventing osteoporosis caused by a bone disease which includes administering to a mammalian subject a therapeutically effective amount of a formulation which is either an HSP antigenic formulation or a bacterial antigenic formulation. The osteoporosis can be caused by a bone disease induced by bone infectious agents such as viruses, bacteria, fungi, protozoa and parasites.

Abstract: A method is provided for attenuating a cytomegalovirus comprising functionally disrupting an open reading frame of a Toledo genome region or its homolog and making chimeric CMV virus genomes.

Abstract: A method is provided for attenuating a cytomegalovirus comprising functionally disrupting an open reading frame of a Toledo genome region or its homolog and making chimeric CMV virus genomes.

Abstract: A method is provided for attenuating a cytomegalovirus comprising functionally disrupting an open reading frame of a Toledo genome region or its homolog and making chimeric CMV virus genomes.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The present invention provides CTL epitope peptides and polyepitope peptides from 14 distinct antigens of human cytomegalovirus (HCMV) that are restricted through HLA the most commonly prevalent class I alleles in different ethnic populations of the world. These epitopes provide an important platform for CTL epitope-based vaccines against HCMV. The present invention further provides vaccine compositions comprising the subject epitope and polyepitope peptides and methods for vaccination of humans and for the adoptive transfer of HCMV-specific T cells to human subjects. The present invention further provides reagents and methods for determining the HCMV status or level of HCMV-specific immunity of a subject.

Abstract: The invention relates to neutralizing antibodies and antibody fragments having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for a combination of hCMV proteins UL130 and UL131A, or for a combination of hCMV proteins UL128, UL130 and UL131A. The invention relates also to immortalized B cells that produce, and to epitopes that bind to, such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies, antibody fragments, and epitopes in screening methods as well as in the diagnosis and therapy of disease.

Abstract: Disclosed are compositions and methods for modulating Epstein-Barr virus (EBV) infection in a patient. The compositions may include peptides or peptidomimetics that are related to gp42 and function to inhibit EBV-mediated membrane fusion.

Abstract: The invention comprises novel polynucleotides, and related vectors, host cells, methods, and compositions, containing transcriptional enhancers providing very high levels of expression of operably-linked expressible nucleic acid sequences in eukaryotic cells. Advantageously the enhancers may be used in combination with their naturally-associated promoters and/or other genetic elements that increase transcription. The invention comprises eukaryotic expression vectors that are capable of providing increased levels of expression in many cell types over that obtainable from human or murine CMV IE enhancer/promoter elements.

Abstract: The present invention relates to novel methods of vaccination and vaccine delivery.

Abstract: The invention provides for a method of enhancing immunological responses to an antigen in a vaccine formulation, and for a vaccine formulation that provides for an enhanced immunological response to an antigen. In the method and formulation the antigen is administered with an adjuvant which adjuvant comprises a solution of nitrous oxide gas in a pharmaceutically acceptable carrier solvent for the gas and which adjuvant includes at least one fatty acid or ester or other suitable derivative thereof selected from the group consisting of oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid [C20: 5?3], decosahexaenoic acid [C22: 6?3], ricinoleic acid and derivatives thereof selected from the group consisting of the C1 to C6 alkyl esters thereof, the glycerol-polyethylene glycol esters thereof and the reaction product of hydrogenated natural oils composed largely of ricinoleic acid based oils, such as castor oil with ethylene oxide.

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 provides a vector encoding a derivative of EBNA-1 that is not cytotoxic when expressed efficiently in cells, which supports extrachromosomal replication, maintenance and transcription from extrachromosomal oriP containing vectors but does not substantially activate transcription from host cell genes. Also provided is a vector having oriP and encoding a derivative of EBNA-1. The vectors of the invention may be employed in vitro and in gene therapy.

Abstract: An immunogenic composition in a dose volume suitable for human use comprising an antigen or antigenic preparation, in combination with an adjuvant which adjuvant comprises an immunologically active saponin fraction derived from the bark of Quillaja Saponaria Molina presented in the form of a liposome and a lipopolysaccharide wherein said saponin fraction and said lipopolysaccharide are both present in said human dose at a level of below 30 ?g.

Abstract: Viruses having weakened ability to establish and/or maintain latency and their use as live vaccines are described. The vaccines have one or more alterations in genes that provide continued virus replication but that inhibit latency. The vaccine materials and methods for their construction are exemplified with the varicella zoster virus. Deletion of a significant portion from both copies of the varicella zoster gene ORF63 was shown to inhibit establishment of a latent infection from a live vaccine form of the virus. Insertion of an additional ORF62 gene which is partially truncated with the ORF63 deletion inhibited establishment of latency and allowed normal growth of the virus. Other desirable viral antigen encoding sequence(s) and/or cytokine genes advantageously may replace deleted genetic material to enhance a desired immunological response. Aspects of the discovery pertain to live vaccines of other viruses, and can provide a variety of vaccines having greater safety.

Abstract: The present invention relates to methods and compositions for preventing or treating diseases of a mammal, including viral infections, wherein at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor present on cells of the mammal to be treated. The invention also provides methods of identifying compositions, wherein the compositions are useful for treating mammalian diseases, including viral infections, for which at least one symptom of the disease is mediated at least in part by the specific binding of an effector molecule to a DC-SIGN receptor present on the cells that express the DC-SIGN receptor, belonging to the mammal to be treated. The invention further relates to compositions and methods for targeting subject molecules to cells that express the DC-SIGN receptor.

Abstract: The invention provides materials and methods for using EBV EBNA2 peptide epitopes to treat and/or prevent post-transplant lymphoproliferative disorders (PTLD). The invention also provides compositions and articles of manufacture containing EBNA2 peptide epitopes that can be used to treat and/or prevent PTLD.

Abstract: The present invention provides methods and compositions comprising a population of alphavirus replicon particles comprising alphavirus replicon RNAs, wherein a first replicon RNA comprises nucleic acid encoding cytomegalovirus pp65 and IE1 protein or immunogenic fragments thereof, and a second replicon RNA comprises nucleic acid encoding cytomegalovirus gB protein or an immunogenic fragment thereof, and wherein each of the two replicon RNAs is contained within a separate alphavirus replicon particle.

Abstract: Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit human CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.

Abstract: Use of an immunogenic composition comprising VZV gE, or immunogenic fragment thereof, and a TH-1 adjuvant in the preparation of a medicament for the prevention or amelioration of shingles and/or post herpetic neuralgia.

Abstract: Phosphorylated glucomannan polysaccharide compositions are shown to effectively enhance healthy immune function. Dosage forms including pills, sprays, functional foods and cosmetics may achieve this benefit while being essentially free of storage protein from nongerminated seeds of Ricinus communis.

Abstract: The present invention relates to the identification of the active domain of Herpoxin, a DNA virus-inhibiting-protein which was isolated from cobra venom in U.S. Pat. No. 5,648,339 and has a molecular weight of 13.5 kDa We have isolated a fragment of Herpoxin which contains the active domain and which we have named Herp. Herp mimics the activity of Herpoxin in inhibiting the replication of DNA viruses. A synthetic version of the active fragment was produced having the amino acid sequence Asn-Leu-Tyr-Gln-Phe-Lys-Asn-Met-Ile-Gln. The synthetic version of Herp consisting of ten amino acids inhibits the replication of DNA viruses such as herpes viruses types 1 and 2, cytomegalovirus and varicella zoster virus as well as Tubercle bacilli.

Abstract: This invention relates to mutated CMVpp65, a viral structural protein which activates cell mediated immunity in humans infected with CMV. The mutations remove undesirable protein kinase activity naturally present in the protein and make it suitable for the production of both DNA and protein vaccines. Therefore, the invention provides proteins and DNAS, as well as vaccines comprising the proteins and DNAs, including cellular vaccines and vectors. Other embodiments of the invention relate to methods of enhancing immune response and vaccinating against CMV, including gene therapy methods and vectors.

Abstract: An isolated protein construct comprising a polyepitope derived from multiple human cytomegalovirus protein antigen epitopes conjugated to an extracellular domain of glycoprotein B, which isolated protein is capable of eliciting a cytotoxic T-lymphocyte immune response as well as a neutralizing antibody response to human cytomegalovirus. Also provided are pharmaceutical compositions comprising the isolated protein or an adenoviral expression construct for delivery and expression of a nucleic acid encoding the isolated protein for prophylactic and/or therapeutic treatment of human cytomegalovirus infection, particularly in humans.

Abstract: Epstein-Barr virus (EBV) specific polypeptides are disclosed. Also disclosed are the use of these polypeptides for the production of polypeptide-specific antibodies and the diagnosis and treatment of EBV-associated disease.

Abstract: The invention provides a method of decreasing viral replication in cells, the method comprising decreasing levels of functional cellular protease in the cells. The invention further provides a method of treating or preventing a viral infection in a subject, the method comprising administering to the subject an amount of a compound effective to decrease levels of functional cellular protease in the cells of the subject.

Abstract: Provided are novel Toledo and Towne human cytomegalovirus DNA sequences (HCMV) and proteins encoded thereby. The sequences are useful in methods and compositions for detecting HCMV infections and in immunogenic compositions for Preventing HCMV infections.

Abstract: A method is provided for attenuating a cytomegalovirus comprising functionally disrupting an open reading frame of a Toledo genome region or its homolog and making chimeric CMV virus genomes.

Abstract: The present invention provides synthetic compounds, antibodies that recognize and bind to these compounds, polynucleotides that encode these compounds, and immune effector cells raised in response to presentation of these epitopes. The invention further provides methods for inducing an immune response and administering immunotherapy to a subject by delivering the compositions of the invention.

Abstract: Data consistent with autoimmune disease being caused by Epstein-Barr virus are shown. Based on this evidence, an effective vaccine would prevent the autoimmune disease in those vaccinated, modified or administered so that the vaccine is not itself capable of inducing autoimmune disease. In the case of anti-Sm, structures to be avoided in an Epstein-Barr virus-derived vaccine have been identified. Differences have been identified in the immune responses to Epstein-Barr infection between individuals who develop a specific autoimmune disease and those who do not. These differences are used to distinguish those who are at greater risk for developing specific autoimmune diseases from those who are a lesser risk. Assuming Epstein-Barr virus causes autoimmune disease and that Epstein-Barr virus remains latent in the patient for life, reactivation of the virus from the latent state is important in generating or maintaining the autoimmune response that culminates in autoimmune disease.

Abstract: A method of designing a new anti-CMV drug is disclosed. In one embodiment, the invention comprises (a) analyzing the binding of glycoprotein O to a glycoprotein O receptor and (b) designing a candidate drug that would competitively interfere with glycoprotein O binding to glycoprotein O receptor and (c) showing that the candidate drug competitively inhibits glycoprotein O binding to glycoprotein O receptor. A method of screening anti-CMV drugs, a vaccine effective to diminish CMV infection, and a method of diminishing CMV infection are also disclosed.

Abstract: Varicella zoster virus (VZV) inimunoreactive protein VP26 and its diagnostic use are described. The invention relates to immunoreactive peptides which are homologous with the region of amino acid positions 12 to 235 (SEQ ID NO: 7) of the varicella zoster virus protein VP26, to nucleic acids which encode these peptides and to the use of the peptides or nucleic acids for diagnosing an infection with varicella zoster virus.

Abstract: An attenuated herpes virus which lacks a functional vhs gene or a functional equivalent thereof, but which has a functional UL43 gene or functional equivalent thereof, stimulates an immune response when dendritic cells are infected with the virus.

Abstract: The present invention relates to compositions for the treatment or prevention of Zoster of individuals infected with Varicella Zoster virus (VZV), and to the prevention and treatment of Varicella infections. The compositions of the invention comprise the protein encoded by VZV gene 63 or an immunologically active derivative thereof. The invention further relates to compositions containing DNA or RNA corresponding to VZV gene 63.

Abstract: A method of stimulating an immune response in a human or animal subject, which method comprises administering to a subject in need thereof an effective amount of an attenuated herpes virus which: (i) lacks a functional vhs gene, or a functional equivalent thereof; (ii) lacks a functional ICP47 gene, or a functional equivalent thereof; and (iii) is incapable of expressing a substantial amount of functional ICP22, or a functional equivalent thereof, in mammalian dendritic cells.

Abstract: Epstein-Barr virus (EBV) specific polypeptides consisting of a series of one to 1000 peptide units selected from the group consisting of peptide units ?, ?, ? and ?, wherein ? is 25 amino acids or less and has the formula (?ETFTETWNRFITHTE?) (SEQ ID NO:1), ? is 25 amino acids or less and has the formula (?GMLEASEGLDGWIHQ?) (SEQ ID NO:2), ? is 25 amino acids or less and has the formula (?HQQGGWSTLIEDNI?) (SEQ ID NO:3), ? is 25 amino acids or less and has the formula (?KQKHPKKVKQAFNPL?) (SEQ ID NO:4), ? and ? are each independently from 0 to 5 naturally occurring amino acids, and the polypeptide is capable of binding antibody in a specimen from an individual with Epstein-Barr virus (EBV)-associated disease are disclosed. Also disclosed are the use of these polypeptides for the production of polypeptide-specific antibodies and the diagnosis and treatment of EBV-associated disease.

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: This invention relates to mutated CMVpp65, a viral structural protein which activates cell mediated immunity in humans infected with CMV. The mutations remove undesirable protein kinase activity naturally present in the protein and make it suitable for the production of both DNA and protein vaccines. Therefore, the invention provides proteins and DNAs, as well as vaccines comprising the proteins and DNAs, including cellular vaccines and vectors. Other embodiments of the invention relate to methods of enhancing immune response and vaccinating against CMV, including gene therapy methods and vectors.