Abstract: A gene vector comprising a miRNA sequence target.

Abstract: The present invention relates to nucleic acid molecules encoding a recombinant human cytomegalovirus (HCMV) strain, dense bodies produced by said HCMV strain and preparations of said dense bodies for use in medicine, particularly as a vaccine against HCMV.

Abstract: The invention relates to an immunogenic composition comprising an HCMV gH/gL/UL128/UL130/UL131 pentameric complex antigen and a TH1-inducing adjuvant. It further relates to the immunogenic composition for use as an HCMV vaccine.

Abstract: The present invention relates to a composition comprising Epstein-Barr Virus (EBV) particles for use in vaccination of a subject, wherein said EBV particles comprise a significantly reduced chromosome instability-inducing EBV polypeptide activity. The present invention also relates to a composition comprising EBV particles for use in vaccination of a subject, wherein said vaccination comprises avoiding contacting the cytosol and/or nucleus of cells of said subject with a chromosome instability-inducing EBV polypeptide activity. Moreover, the present invention relates to polynucleotides, host cells, methods, and uses related to the aforesaid compositions.

Abstract: Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir-sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

Abstract: The present invention relates to variants of herpes simplex virus (HSV) that selectively infect and replicate in cancer cells, including HSV strains that selectively infect and replicate in bladder cancer cells. Preferred HSV of the invention have intact endogenous Us11 and Us12 genes and have genes encoding ICP34.5 replaced with a gene encoding Us11 fused to an HSV immediate early (IE) promoter. The variant HSV of the invention also comprise one or more additional heterologous genes encoding immunomodulatory polypeptides. Methods and compositions using these variant HSV, for example, for treating cancer in a subject, are also provided.

Abstract: Provided herein is a bee venom composition with effects of protecting and beautifying lips, comprising cosmetic matrix components for use on lips and bee venom. The bee venom is prepared by using the following method: crude bee venom is dissolved with water, before ultrafiltrated using an ultrafiltration membrane with the molecular weight cutoff 10000 Da, and then the resulting filtrate is freeze-dried to obtain the bee venom.

Abstract: The present disclosure provides methods useful for determining levels of HCMV infection in host cells and, by extension, determining levels of neutralizing antibodies present in a sample. The present disclosure encompasses the recognition that HCMV viruses that have a fluorescent moiety permit detection of viral infection (e.g., by assessing fluorescence in cells after contacting the host cell with the virus). In some embodiments, levels of HCMV infection are determined by fluorescence detection where the virus has been preincubated with a test sample (e.g., a serum sample) from a subject. In some embodiments, the subject has been administered a candidate HCMV vaccine.

Abstract: Provided are an ORF7 deficient varicella virus, an vaccine comprising the virus and use thereof, as well as a method for the production the virus.

Abstract: Compositions and methods related to live or live attenuated pre-conditioned and typical viruses such as rotaviruses are disclosed. The live attenuated rotaviruses exhibit better stability characteristics and are useful for the prevention of a rotavirus infection and/or rotavirus gastroenteritis in children.

Abstract: The present invention relates to an Epstein-Barr virus-like particle (EB-VLP) substantially free of Epstein-Barr Virus (EBV) DNA. The present invention also relates to a polynucleotide comprising an EBV genome a) lacking at least one expressible gene selected from the group consisting of the BFLF1 gene, the BBRF gene, the BGRF1 gene, the BDRF1 gene, the BALF3 gene, the BFRF1A gene, and the BFRF1 gene, and b) producing the EB-VLP of the invention in a suitable host cell. The present invention further relates to a vector and a host cell comprising the polynucleotide of the invention as well to a method of manufacturing the EB-VLPs, a method of manufacturing a vaccine thereof, a vaccine and a composition comprising the EB-VLPs.

Abstract: The present disclosure provides a method to prepare purified enveloped viral particle preparations employing ion exchange chromatography and tangential flow filtration.

Abstract: The present invention discloses an ex vivo method for producing a preparation containing CD4+ T cells specific for EBV structural antigens for use in the prophylaxis and treatment of patients with a reduced T cell activity in order to prevent or treat growth of EBV infected B cells.

Abstract: The invention relates to a method of producing an influenza virus H5 polypeptide in a plant comprising the steps of cloning an influenza H5 gene or nucleic acid encoding its functional equivalent into a vector adapted to target components present in the plant, infiltrating at least a portion of the plant with the vector or transforming plant tissue with the vector so as to transiently express the influenza virus H5 polypeptide, and/or to create a transgenic plant; and recover the influenza virus H5 polypeptide expressed by the plant. The invention further relates to vectors, transgenic plants or parts thereof and the progeny of such plants used in or which come about as a result of the method.

Abstract: The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided.

Abstract: The present disclosure provides inter alia compositions that comprise therapeutic agents (e.g., live attenuated viral antigens, therapeutic proteins, etc.) and a lipid component. The lipid component may comprise or consist of different types of lipid or lipids as described herein. In some embodiments the therapeutic agents are thermolabile. The present disclosure also provides methods for preparing compositions, including the aforementioned compositions (e.g., melt methods and spray injection methods among others).

Abstract: An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

Abstract: The present invention relates to methods and compositions for use in inducing tumor-specific antibody mediated complement-dependent cytotoxic response in an animal having a tumor comprising administering to said animal a composition comprising a replication competent oncolytic virus wherein administration of the composition induces in the animal production of antibodies that mediate a CDC response specific to said tumor.

Abstract: The present invention provides improved treatment methods by the administration of both an inhibitor of indoleamine-2,3-dioxygenase in addition to the administration of an additional therapeutic agent.

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: A BHV-1 mutant virus has been made that incorporates into a single virus two or more deletions in one or more of three genes—glycoprotein N, glycoprotein E and Us9. Specifically, a BHV-1 UL49.5?30-32 CT-null virus was made and tested. This mutant virus was then used to incorporate additional changes, e.g., the glycoprotein E cytoplasmic-tail deletion, the Us9 deletion, or both. This triple mutant BHV-1 UL49.5?30-32 CT-null/gE CT?/Us9? virus will be superior to the current BHV-1 mutants because the mutant virus will not be shed following reactivation, will be a DIVA based on gE CT-specific serum antibodies, and will induce better protective response by inducing higher SN titers and better cellular immune response. This new virus will have sufficient viral replication in the nasal epithelium and will be a good vaccine for protection of cattle from BHV-1. The new mutant viruses can also be used as vectors for exogenous genes.

Abstract: Embodiments of the invention provide methods, monoclonal antibodies, polyclonal antibodies, assays, and kits for detecting HPV infection and HPV related cancer diagnosis, including infection by various HPV genotypes, early and/or late stage HPV-associated or HPV-specific cancers. Various monoclonal antibodies recognizing specific epitope for specific HPV protein or HPV type, common epitope for various HPV proteins or HPV types are obtained. These obtained monoclonal antibodies are useful tools in early clinical detection of HPV infection and general detection of HPV related diseases, specific detection of invasive cervical cancer, detection of other HPV related cancers, early stage precancerous lesions as well as late stage cancer progression.

Abstract: Embodiments of the invention provide methods, monoclonal antibodies, polyclonal antibodies, assays, and kits for detecting HPV infection and HPV related cancer diagnosis, including infection by various HPV genotypes, early and/or late stage HPV-associated or HPV-specific cancers. The anti-HPV antibodies are used in performing immunological assays on clinical samples. Various immunological assays and kits for detecting HPV infection, cervical cancer, other HPV related cancers, early stage precancerous lesions as well as late stage cancer progression are also provided.

Abstract: Provided herein are methods and compositions for stabilization of active agents. The active agents are distributed, mixed or embedded in a silk fibroin matrix, thereby retaining the bioactivity of the active agents upon storage and/or transportation. In some embodiments, the storage-stable vaccine-silk compositions are also provided herein.

Abstract: The present invention relates to a vaccine comprising a particle, said particle comprising (i) at least one Epstein-Barr virus (EBV) structural polypeptide, (ii) at least one EBV lytic polypeptide, (iii) membrane lipids, said particle being devoid of EBV DNA, wherein (a) the B-cell transformation capacity of one or more EBV polypeptides required for B-cell transformation as comprised in said particle is disabled while their immunogenicity is maintained; and/or (b) said particle is devoid of one or more EBV polypeptides required for B-cell transformation. Furthermore, the invention relates to a method for generating a particle, to a cell obtained in the method of the invention, a kit comprising the vaccine or the particle generated according to the method of the invention. Also, the invention relates to the use of the vaccine or the particle generated according to the method of the invention for generating CD8+ cells specific for an EBV antigen.

Abstract: Methods are disclosed for producing defective ribosomal products (DRiPs) in blebs (DRibbles) by contacting cells with a proteasome inhibitor, and in some examples also an autophagy inducer, thereby producing treated cells. DRibbles can be used to load antigen presenting cells (APCs), thereby allowing the APCs to present the DRiPs and antigenic fragments thereof. Immunogenic compositions that include treated cells, isolated DRibbles, or DRibble-loaded APCs are also disclosed. Methods are also provided for using treated cells, isolated DRibbles, or DRibble-loaded APCs to stimulate an immune response, for example in a subject. For example, DRibbles obtained from a tumor cell can be used to stimulate an immune response against the same type of tumor cells in the subject. In another example, DRibbles obtained from a pathogen-infected cell or cell engineered to express one or more antigens of a pathogen can be used to stimulate an immune response against the pathogen in the subject.

Abstract: The invention relates to neutralizing antibodies, and antibody fragments thereof, having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for one, or a combination of two or more, hCMV gene UL products. The invention also relates 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, prevention, and therapy of disease.

Abstract: The invention relates to the production of dense bodies (DB) and to a pharmaceutical composition containing DB.

Abstract: A first composition comprising a ligand part being able to specifically bind to a target, the target being on a diseased cell of an organism, and an epitope part having a non-self epitope, or encoding a non-self epitope, the non-self epitope not naturally being encoded by the organism, wherein the target is internalized after forming a complex with the composition and the non-self epitope is presented on the cell surface of said diseased cell of an organism after internalization.

Abstract: The present invention is directed towards compositions comprising Ii-Key/HPV hybrid peptides. The hybrid peptides of the present invention are effective in the generation of CD4+ helper T cell immune responses directed towards the specific HPV epitopes encoded in the hybrid peptide. The inclusion of the Ii-key peptide in the hybrid causes the peptide to have greater immunogenicity as compared to control peptide. The inclusion of Ii-Key/HPV hybrid in a peptide vaccine formulation composing both HPV hybrid and HPV CTL epitope peptide (administered concurrently or sequentially) leads to a greater CTL activity against HPV CTL epitopes. The hybrid peptides of the present invention may be useful, for example, for the immunization of subjects against HPV.

Abstract: The invention relates to an expression system comprising polynucleotides encoding proteins, wherein the expression system comprises a first polynucleotide encoding at least one protein, peptide or variant thereof, which induces a T cell response, and a second polynucleotide encoding at least one protein peptide or variant thereof, which induces an anti-pathogenic B cell response. The invention further relates to protein mixtures encoded by the expression system and cells comprising the expression system or the protein mixture and pharmaceutical compositions comprising the expression system or the protein mixture. The expression system, polynucleotides, proteins, cells, and pharmaceutical compositions are useful in the prophylaxis or treatment of infections. The invention further relates to nucleotide constructs which comprises, essentially consists or consists of a polynucleotide encoding a modified influenza hemagglutinin (HA).

Abstract: The present disclosure provides an isolated or purified guinea pig cytomegalovirus (GPCMV) Strain CIDMTR, glycoproteins from GPCMV Strain CIDMTR, and methods of use thereof.

Abstract: Provided are a full genome DNA of a human cytomegalovirus (HCMV) strain JHC isolated from Korean patients and open reading frames (ORFs) thereof and, more particularly, UL1, UL119 and RL6.

Abstract: The present invention provides methods and compositions for treating and/or preventing a cytomegalovirus infection in a subject, comprising administering to the subject an effective amount of a cytomegalovirus IL-10 protein modified to have reduced functional activity while retaining immunogenicity. The present invention further provides nucleic acid molecules encoding a cytomegalovirus IL-10 protein or fragment thereof of this invention as well as vectors comprising such nucleic acids. Also provided herein are neutralizing antibodies that specifically bind cmvIL-10.

Abstract: The invention relates to plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens, which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of any of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods of inducing an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

Abstract: The invention relates to immunotherapeutic compounds and to methods for stimulating an immune response in a subject individual at risk for developing cancer, diagnosed with a cancer, in treatment for cancer, or in post-therapy recovery from cancer or the compounds of the invention can be administered as a prophylactic to a subject individual to prevent or delay the development of cancer.

Abstract: The present invention provides a new means of restoring the immune system in aging and immunocompromised individuals using an antioxidant nutraceutical. The nutraceutical stimulates the aging immune system through the Nrf2 master gene regulatory pathway. The invention is based in part on the discovery that the Nrf2 has antioxidant and immune restorative activity. The nutraceutical improves function of both the innate and adaptive immune systems.

Abstract: The invention relates to neutralizing antibodies, and antibody fragments thereof, having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for one, or a combination of two or more, hCMV gene UL products. The invention also relates 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, prevention, and therapy of disease.

Abstract: The present disclosure provides methods for preparing vesicles. In one aspect, the methods involve providing a molten mixture of vesicle-forming lipids and adding the molten mixture of vesicle-forming lipids to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed, wherein in the step of adding the molten mixture of vesicle forming lipids is at a temperature of less than 120° C. In another aspect, the methods involve providing a molten mixture of vesicle-forming lipids and adding an aqueous solution comprising an antigen to the molten mixture of vesicle-forming lipids such that antigen-containing vesicles are formed, wherein the resulting mixture is placed under temperature-controlled conditions of less than 60° C. In yet another aspect, the methods involve providing a solution of vesicle forming lipids and adding the solution of vesicle-forming lipids to an aqueous solution comprising an antigen by injection such that antigen-containing vesicles are formed.

Abstract: A non-mammalian transfer factor, compositions including the non-mammalian transfer factor, and methods for generating and preparing the non-mammalian transfer factor. The non-mammalian transfer factor may have specificity for one or more antigens. A method of using the non-mammalian transfer factor includes administering either antigen-specific non-mammalian transfer factor or antigen non-specific non-mammalian transfer factor to mammals to treat or prevent pathogenic infections in the mammals.

Abstract: The present invention relates to methods and compositions for inhibiting the entry of viruses, such as herpesviruses into a host cell. A conserved viral integrin-binding gB disintegrin-like domain has been identified that engages integrins and facilitates viral internalization into the host cell. Therefore, methods and compositions, such as antiviral agents encompassing the conserved gB disintegrin-like domain and antibodies thereto are described. These active agents interfere with the interaction between virions and cellular integrins, thereby inhibiting viral infection of a host cell.

Abstract: A vaccine comprising an immunologically effective amount of recombinant modified vaccinia Ankara (rMVA) virus which is genetically stable after serial passage and produced by a) constructing a transfer plasmid vector comprising a modified H5 (mH5) promoter operably linked to a DNA sequence encoding a heterologous foreign protein antigen, wherein the expression of said DNA sequence is under the control of the mH5 promoter; b) generating rMVA virus by transfecting one or more plasmid vectors obtained from step a) into wild type MVA virus; c) identifying rMVA virus expressing one or more heterologous foreign protein antigens using one or more selection methods for serial passage; d) conducting serial passage; e) expanding an rMVA virus strain identified by step d); and f) purifying the rMVA viruses from step e) to form the vaccine.

Abstract: The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an attenuated or inactivated virus in combination with a non-ionic surfactant vesicle (NISV).

Abstract: The present invention relates to a pharmaceutical vaccine composition comprising: (a) a pathogen-derived antigen selected from the group consisting of Mycobacterium tuberculosis antigen, Bacillus anthracis antigen, HAV (hepatitis A virus) antigen, HBV (hepatitis B virus) antigen, HCV (hepatitis C virus) antigen, HIV (human immunodeficiency virus) antigen, influenza virus antigen, HSV (herpes simplex virus) antigen, Hib (Haemophilus influenzae type b) antigen, Neisseria meningitidis antigen, Corynebacterium diphtheriae antigen, Bordetella pertussis antigen, Clostridium tetani antigen and Varicella virus antigen; (b) a deacylated non-toxic LOS (lipooligosaccharide); and (c) a pharmaceutically acceptable carrier.

Abstract: The present invention relates to a process for stabilizing an adjuvant containing vaccine composition, an adjuvanted vaccine composition in dry form and in particular a process for stabilizing an influenza vaccine composition, particularly an adjuvanted influenza vaccine composition in dry form.

Abstract: The invention relates to neutralizing antibodies which are specific for human cytomegalovirus and bind with high affinity as well as immortalized B cells that produce such antibodies. The invention also relates to the epitopes that the antibodies bind to as well as the use of the antibodies and the epitopes in screening methods as well as the diagnosis and therapy of disease.

Abstract: Compositions and methods of activating dendritic cells with LMP1 and LMP1-activated dendritic cell based compositions and methods are effective for dendritic cell therapy and provide an adjuvant function for vaccine administration. LMP1 or LMP1-CD40 chimeric protein may be used to activate and mature dendritic cells. LMP1 and LMP1-activated dendritic cells act as an adjuvant to enhance the cellular immune response. Also disclosed herein are kits for activating dendritic cells and for preparing a vaccine formulation. Administration of the dendritic cells transfected with LMP1 can induce an immune response against cancer or infection. The mature dendritic cells may comprise an antigen and at least one cytokine in addition to LMP1.

Abstract: The invention relates to a method of producing a HPV polypeptides and/or an influenza virus H5 polypeptide in a plant comprising the steps of cloning a HPV gene; and/or an influenza virus H5 gene or nucleic acid encoding their functional equivalents into a vector adapted to target components present in the plant, infiltrating at least a portion of the plant with the vector or transforming plant tissue with the vector so as to transiently express the HPV polypeptides and/or an influenza virus H5 polypeptide, and/or to create a transgenic plant; and recovering the HPV polypeptides and/or an influenza virus H5 polypeptide expressed by the plant. The invention further relates to vectors, transgenic plants or parts thereof and the progeny of such plants used in or which come about as a result of the method.

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: The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided.