Abstract: The disclosure relates generally to alpha polyglutamated methotrexate, formulations containing liposomes filled with alpha polyglutamated methotrexate, methods of making the alpha polyglutamated methotrexate and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated methotrexate and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Abstract: The disclosure relates generally to gamma polyglutamated pralatrexate compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated pralatrexate, and methods of making and using the gamma polyglutamated pralatrexate compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis).

Abstract: The present disclosure provides nucleic acid compositions that incorporate one or more halouracil molecules. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within a microRNA nucleotide sequence with a 5-halouracil increases the ability of the micro-RNA to inhibit cancer progression and tumorigenesis. As such, the present disclosure provides various nucleic acid (e.g., microRNA) compositions having 5-halouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.

Abstract: The present invention relates to prime-boost regimens that involve the administration of at least one mRNA construct, such as the use of such constructs in “boost” administration subsequently to “prime” administration of certain other antigenic composition(s). Such inventive regimens may, in particular, be useful for the induction of an immune response in a subject, and/or the vaccination of such subject against infection from one or more pathogens, and/or the treatment or prevention of one or more diseases or conditions, including a tumour or cancer, allergy or autoimmune conditions, and/or a disease or condition associated with infection from a pathogen. The present invention further describes methods, uses, vaccination compositions, kits and packaged vaccine components related to or useful for one or more of such regimens.

Abstract: Provided in the present invention is the use of the miR-338 cluster as a marker of postmenopausal osteoporosis. In the present invention, it was found that the miR-338 cluster such as miR-338-3p and/or miR-3065-5p are highly expressed in patients with postmenopausal osteoporosis, and it can be used as a marker of postmenopausal osteoporosis, used for preparing an auxiliary diagnostic kit for postmenopausal osteoporosis, which can specifically detect the expression level of the miR-338 cluster in tissues, and is used for non-invasive and early auxiliary diagnosis of postmenopausal osteoporosis in clinic. In addition, inhibitors of the miR-338 cluster have the efficacy of promoting osteogenesis and can be used for treating or preventing postmenopausal osteoporosis.

Abstract: The present invention is directed to Herpes simplex-2 viruses that may be used in vaccines to immunize patients against genital herpes.

Abstract: The present disclosure relates, in part, to pharmaceutical compositions comprising one or more polynucleotides suitable for enhancing, increasing, augmenting, and/or supplementing the levels of Collagen alpha-1 (VII) chain polypeptide and/or Lysyl hydroxylase 3 polypeptide and/or Keratin type I cytoskeletal 17 polypeptide in a subject. The present disclosure also relates, in part, to pharmaceutical compositions and methods of use for providing prophylactic, palliative, or therapeutic relief of a wound, disorder, or disease of the skin in a subject, including a subject having, or at risk of developing, one or more symptoms of epidermolysis bullosa.

Abstract: The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule-encoding gene.

Abstract: Recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such, and methods of use thereof are each provided.

Abstract: The invention provides HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: This invention relates to therapeutic compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The methods are particularly effective for protecting mammals from herpes simplex virus.

Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection, including epitopes confirmed to be recognized by T-cells derived from herpetic lesions. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: The present invention relates to a vaccination strategy that establishes protective immunity, including a protective memory T-cell population.

Abstract: The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Abstract: Compositions are provided in which dendrimers and/or nanoparticles are synthesized with multi-photon responsive elements and self-immolative oligomers. The compositions may be utilized to selectively deliver Payloads within tissue by irradiating the compositions. The compositions may also be used to amplify sensitivity to irradiation.

Abstract: Methods for producing a protein extract from cells, such as cells containing viral proteins, are provided. In general terms, the methods involve: increasing the pH of the cells to a pH of at least about pH 10.0 to produce an intermediate composition, and then, in the presence of a non-ionic detergent, neutralizing the pH of the intermediate composition to produce the protein extract. Kits and compositions for practicing the subject methods are also provided.

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: Contemplated compositions, devices, and methods are drawn to various antigens from Herpes Simplex Virus type 1 (HSV-1) and Herpes Simplex Virus type 2 (HSV-2) and their use in vaccines, therapeutic agents, and various diagnostic tests. In particularly preferred aspects, the antigens are immunodominant and have quantified and known relative reactivities with respect to sera of a population infected with the pathogen, and/or have a known association with a disease parameter.

Abstract: A recombinant herpes virus showing high antitumor activity is provided. In particular, a recombinant herpes simplex virus that expresses an ICP6 gene under control of a tumor-specific promoter or tissue-specific promoter on the genome of the virus is provided.

Abstract: This invention relates to therapeutic compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The methods are particularly effective for protecting mammals from herpes simplex virus.

Abstract: This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV gD2, VP11/12, and VP13/14 polypeptides.

Abstract: This invention relates to therapeutic compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The methods are particularly effective for protecting mammals from herpes simplex virus.

Abstract: The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells render the HSV particles. particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor.

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

Abstract: This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV gD2 polypeptides.

Abstract: This invention provides methods of treating, suppressing, inhibiting, reducing an incidence, reducing the pathogenesis of, ameliorating the symptoms of, or ameliorating the secondary symptoms of a primary or recurring Herpes Simplex Virus (HSV) infection, or prolonging the latency to a relapse of an HSV infection, and disorders and symptoms associated with same and inducing an anti-HSV immune response in a subject comprising the step of contacting the subject with a composition comprising a mutant HSV strain comprising an inactivating mutation in a Us8 gene, followed by a second contacting with the composition.

Abstract: The present invention is directed to the generation of attenuated viruses or viral transcripts for the production of vaccines by incorporating microRNA binding sites within the viral target sequence of the pathogen.

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: This invention provides methods of vaccinating a subject against a Herpes Simplex Virus (HSV) infection and disorders and symptoms associated with same, and impeding, inhibiting, reducing the incidence of, and suppressing HSV infection, neuronal viral spread, formation of zosteriform lesions, herpetic ocular disease, herpes-mediated encephalitis, and genital ulcer disease in a subject, comprising the step of contacting the subject with a mutant strain of the HSV, containing an inactivating mutation in a gene encoding a gE, gI, Us9, or other proteins.

Abstract: The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Abstract: The present invention is directed to Herpes simplex-2 viruses that may be used in vaccines to immunize patients against genital herpes.

Abstract: This invention provides methods of treating, suppressing, inhibiting, reducing an incidence, reducing the pathogenesis of, ameliorating the symptoms of, or ameliorating the secondary symptoms of a primary or recurring Herpes Simplex Virus (HSV) infection, or prolonging the latency to a relapse of an HSV infection, and disorders and symptoms associated with same and inducing an anti-HSV immune response in a subject comprising the step of contacting the subject with a composition comprising a mutant HSV strain comprising an inactivating mutation in a Us8 gene, followed by a second contacting with the composition.

Abstract: This invention relates to therapeutic compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The methods are particularly effective for protecting mammals from herpes simplex virus.

Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are antigens and/or their constituent epitopes confirmed to be recognized by T-cells derived from herpetic lesions or from uterine cervix. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: This invention relates to therapeutic compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The methods are particularly effective for protecting mammals from herpes simplex virus.

Abstract: This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV gD2, VP11/12, and VP13/14 polypeptides.

Abstract: This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV VP11/12 polypeptides.

Abstract: This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV gD2 polypeptides.

Abstract: This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV VP13/14 polypeptides.

Abstract: The present invention is directed to Herpes simplex-2 viruses that may be used in vaccines to immunize patients against genital herpes.

Abstract: A mutant herpesvirus that has a mutated gene that encodes a mutant infected cell protein 0 (ICP0) can be used in therapeutic methods as well as in diagnostics and research experiments. The encoded mutant ICP0 protein can be altered in one or more regions of ICP0 that are substantially conserved between two or more herpesviruses and/or within a phosphorylation region. The mutant herpesvirus can be substantially avirulent and immunogenic.

Abstract: Disclosed are a recombinant DNA molecule encoding a fusion protein comprising a SlpA chaperone and a target polypeptide wherein human FK506 binding proteins (FKBPs) are excluded as target polypeptides, a corresponding expression vector encoding said fusion protein as well as host cells transformed with said expression vector. Also disclosed are a method for producing the fusion protein, a recombinantly produced fusion protein comprising a SlpA chaperone and a target polypeptide. A further aspect of the invention is the use of the recombinantly produced fusion protein, and a reagent kit containing a recombinantly produced fusion protein comprising a SlpA chaperone and a target polypeptide.

Abstract: Provided herein are, inter alia, vaccines and methods of using the same for the treatment or prevention of Herpesvirus infections.

Abstract: Provided herein are methods and compositions for use in treating HSV-related conditions and diseases.

Abstract: The present invention relates to the use of a fully human antigen binding fragment of an antibody for the manufacture of a medicament for the treatment or diagnosis of an ocular disease upon topical administration. The invention further relates to a pharmaceutical composition comprising a fully human binding fragment of an antibody for ocular topical administration for treatment or diagnosis of an ocular disease. In particular, the antibody neutralizes HSV1 and HSV2.

Abstract: The present invention provides methods and compositions for the stimulation of immune responses. In particular, the present invention provides immunogenic nanoemulsion compositions and methods of administering the same (e.g., via a heterologous prime/boost protocol (e.g., utilizing the same nanoemulsion in each the prime and boost administrations)) to induce immune responses (e.g., innate and/or adaptive immune responses (e.g., for generation of host immunity against an environmental pathogen)). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

Abstract: The present invention provides a herpes virus with improved oncolytic properties which comprises a gene encoding an immunomodulatory cytokine and which lacks a functional ICP34.5 gene and a functional ICP47 encoding gene.

Abstract: The invention provides an agent for preventing or treating a condition characterised by the presence of unwanted cells, the agent comprising: (i) a targeting moiety that is capable of targeting to the unwanted cells; and (ii) a T cell antigen, wherein the T cell antigen can be released from the targeting moiety by selective cleavage of a cleavage site in the agent in the vicinity of the unwanted cells.

Abstract: Herpes Simplex Virus-2 (HSV-2) infection is a major health concern. The present disclosure provides, inter alia, certain highly effective vaccines and immunogenic compositions against HSV-2. The antigens can be used therapeutically or prophylactically.

Abstract: The invention provides HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.