Abstract: The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefitting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

Abstract: The present invention relates to therapeutic combinations and methods for treating cancers using combination therapy.

Abstract: Provided herein are chimeric hemagglutinin (HA) polypeptides and uses thereof for inducing an immune response (e.g., an antibody response) against influenza virus. Also provided herein are methods of generating antibodies to the chimeric HA polypeptides in a subject.

Abstract: Attenuated G9P[6] rotavirus is disclosed herein. In some embodiments, pharmaceutical compositions are disclosed that include an attenuated G9P[6] rotavirus, or a component thereof. These compositions can be used to induce an immune response, such as a protective immune response, to a rotavirus. The compositions can be used as vaccines, such as for children (infants), for example in a prime boost strategy.

Abstract: The invention relates to a nucleic acid encoding a polypeptide comprising a plurality of conserved peptide sequences, or variants thereof, wherein the conserved sequences are conserved across one or more HPV genotypes 16, 18, 31, 52, 53, and 58; and wherein the polypeptide comprises a conserved peptide sequence of each of the HPV proteins E1, E2, E4, E5, E6, and E7; and associated vaccines, viral vectors, treatment and prophylaxis.

Abstract: The invention relates to a polynucleotide encoding a polypeptide based on the minimum region of the Orthoreovirus muNS protein that can form inclusions in the endoplasmic reticulum, and to said polypeptide. The invention also relates to a purification method and a method for detecting interaction between two polypeptides based on the capacity of some regions of the Orthoreovirus muNS protein to incorporate themselves into the inclusions, together with a peptide of interest.

Abstract: Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.

Abstract: The invention provides a recombinant Bacillus subtilis, construction method and use thereof, wherein the cell's own FMMs are used as a space scaffold, and a multi-enzyme complex is constructed from specific marker proteins FloA and FloT, such that an artificial substrate channel is formed, and the cell metabolic burden is effectively reduced. The recombinant Bacillus subtilis of the invention can efficiently synthesize GlcNAc without affecting cell life activity, and can also limit the toxic intermediate metabolite GlcN-6-P near the plasma membrane to reduce or eliminate its inhibition on cell activity. In the process of shaking flask fermentation using complex medium, the yield of acetyl glucosamine of the control strain BSG-C was only 0.45 g·L?1, while that of BSG-AT, BSG-ATP, BSG-ATPB increased to 5.29 g·L?1, 6.22 g·L?1 and 8.48 g·L?1 respectively. The construction method of recombinant Bacillus subtilis is simple, easy to use and has a good application prospect.

Abstract: Disclosed herein are virus-like particle (VLP)-based bivalent vaccine compositions. The compositions may comprise a spherical retroviral Group—specific Antigen (“Gag”) protein core and at least two Ebola glycoproteins. The at least two Ebola glycoproteins may be located at the exterior surface of the spherical Gag protein core, such that the VLP-based vaccine presents at least two Ebola glycoprotein antigens. In one aspect, the at least two Ebola glycoproteins are a Zaire (EBOV) glycoprotein, and a Sudan (SUDV) glycoprotein.

Abstract: The present invention relates to field of live attenuated recombinant tetravalent dengue vaccines and methods of producing stable compositions. Present invention specifically relates to a stable composition and methods of using such a stable composition comprising live attenuated recombinant dengue virus, stabilizer, bulking agent and optionally buffering agents, wherein the live attenuated dengue virus is generated from ? 30 and or ? 31 deleted or mutated dengue strains. More specifically, the present invention relates to stabilizers for freeze-dried live attenuated immunogenic and/or vaccine compositions that may comprise, inter alia, dengue virus(es). The invention further relates to stabilized, freeze-dried live attenuated immunogenic and/or vaccine compositions of, dengue virus(es), which may contain these stabilizers. Other aspects of the invention are described in or are evident from the following disclosure, and are within the ambit of the invention.

Abstract: Provided herein are, inter alia, methods and compositions including T cells expressing (i) a recombinant CAR protein which includes a peptide binding site and is capable of specifically binding cancer-specific antigens and (ii) a T cell receptor specific for a viral antigen (e.g., a CMV pp65 protein). The engineered T cells provided herein may be used in combination with a viral vaccine (e.g. cytomegalovirus (CMV) Triplex Vaccine) to treat a variety of cancers. The methods described herein also permit in viva expansion of CMV-specific CAR T cells, instead of or in addition to ex vivo expansion, avoiding excessive T cell exhaustion that results in some cases from ex vivo manufacturing.

Abstract: The invention relates to a method for determining the cell mediated immune competence of a subject. The method comprises conducting a cell-mediated immunoassay (CMI) on a sample comprising immune cells from a subject. The method further comprises detecting in vitro an immune response to a pool of peptides, wherein the pool of peptides is derived from at least three viral antigens.

Abstract: The invention relates to a vaccine comprising live attenuated recombinant alphavirus comprising mutated capsid protein. The invention also relates to a method of preventing a subject from contracting an alphaviral infection that would otherwise produce clinical signs of disease. In an embodiment the mutated capsid protein is Chikungunya virus (CHIKV) capsid protein having a mutated nucleolar localisation signal/sequence (NoLS), preferably the mutant NLS 101/95.

Abstract: The present invention relates to compositions and methods for the treatment and prevention of canine influenza virus (CIV) and CIV-related pathology. The present invention is based in part upon the discovery that various mutations in segment 1 and segment 2 of the CIV genome, thereby encoding mutant PB2 and PB1 protein, render the virus to be temperature-sensitive.

Abstract: An isolated protein comprises respective amino acid sequences of each of a plurality of CTL epitopes from two or more different herpesvirus antigens and further comprises an intervening amino acid or amino acid sequence between at least two of said CTL epitopes comprising proteasome liberation amino acids or amino acid sequences and, optionally, Transporter Associated with Antigen Processing recognition motifs. The isolated protein is capable of rapidly expanding human cytotoxic T lymphocytes (CTL) in vitro and eliciting a CTL immune response in vivo upon administration to an animal as an exogenous protein. Typically, the isolated protein comprises no more than twenty (20) CTL epitopes derived from cytomegalovirus and/or Epstein-Barr virus antigens.

Abstract: The present invention relates to a vaccine composition comprising a multimeric complex of Herpes Simplex Virus (HSV) polypeptides for the treatment or vaccination against HSV. The present invention also relates to a vector comprising a polynucleotide encoding the HSV polypeptides and a host cell comprising the vector. The present invention further comprises a method for producing the vaccine composition.

Abstract: The present invention provides systems and methods for performing forward genetic screens in cells and methods of treating disease through inhibiting targets identified in a forward genetic screen as involved in a pathway associated with the disease. The invention involves the use of multiple tandem fluorescent reporter molecules separated by cleavage sites under the control of a single promoter to enhance the fluorescent readout from a cell screen.

Abstract: Disclosed herein are methods and compositions for identifying and/or treating subjects having or likely to have amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). Antibodies specific for one or more di-amino acid repeat-containing proteins are also provided herein.

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

Abstract: The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (“O interface”); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (“L domain”); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (“M domain”), as well as membrane-enveloped versions of the multimeric assemblies.

Abstract: The present invention provides a myricetin derivative, a preparation method thereof, a pharmaceutical composition containing the same, an application thereof for treating colitis, preventing and treating colitis-associated tumorigenesis and treating colorectal cancer, and an application thereof in preparing a composition for modulating activities of endoplasmic reticulum stress signaling molecules. The myricetin derivative disclosed herein has excellent water solubility, and has biological activities including inhibition of colitis, prevention and treatment of colitis-associated tumorigenesis, and treatment of colorectal cancer. The preparation method disclosed herein uses myricetrin as starting material which is economical and easily available. With the merits of low cost, high yield, high product purity and suitability for large-scale industrial production, the preparation method disclosed herein represents significant market value and economic prospects.

Abstract: The present invention describes an additive for accelerating hybridization comprising: a) an aqueous solution of sodium dextran sulphate, b) a salt, c) a buffer system, d) a strong mineral base possibly mixed with at least one polar aprotic solvent, or at least one polar aprotic solvent. The additive described herein enables a reduction in the time required to perform the investigations with molecular probes on histological and cytological samples; the possibility of applying it to the protocol already in use in the routine practices of various laboratories in order to reduce the working time of histological and cytological samples for investigations with molecular probes, with no organisational impacts on the operators' work, enabling a more rapid diagnostic response for the patient and offering the possibility of using the additive described herein without formamide.

Abstract: The present invention pertains to a vaccine for use in prophylactically treating an animal against an infection with porcine circovirus type 2 (PCV2) and an infection with PRRS virus, the vaccine comprising in combination non-replicating immunogen of porcine circovirus type 2 and live attenuated PRRS virus, wherein the vaccine additionally comprises albumin.

Abstract: Co-administration (for example, immunogenic cocktail compositions and/or prime boost regimens) of computationally optimized H1N1 influenza hemagglutinin (HA) polypeptides is provided. Coadministration of the optimized H1N1 influenza hemagglutinin (HA) polypeptides facilitates synergistic neutralization of viral infection and provides for improved protective immunity (for example, a broad reactive immune response) to diverse and multiple H1N1 influenza virus strains, including both seasonal and pandemic strains.

Abstract: The disclosure provides methods for generating an optimized nucleotide sequence encoding an engineered influenza structural protein and the optimized nucleotide sequences obtained therefrom. The optimized nucleotide sequences can be used in a reverse genetics system to facilitate the rescue of infectious influenza virus containing the engineered structural proteins and/or enhance viral titers. Also provided are methods of preparing an influenza vaccine composition using the optimized nucleotide sequences, as well as methods of inducing an immune response using the influenza vaccine composition.

Abstract: Disclosed herein is a vaccine comprising an antigen and CD40L. Also disclosed herein are methods for increasing an immune response in a subject. The methods may comprise administering the vaccine to the subject in need thereof.

Abstract: The disclosure discloses a porcine epidemic diarrhea virus S protein and a subunit vaccine thereof as well as a method for preparing the subunit vaccine and application thereof. The vaccine contains 30˜220 ?g of a recombinant porcine epidemic diarrhea virus S protein and a pharmaceutically acceptable ISA 201 VG adjuvant. A method for preparing the subunit vaccine comprises the following steps: (1) cloning the recombinant porcine epidemic diarrhea virus S protein; (2) expressing and purifying the recombinant porcine epidemic diarrhea virus S protein; (3) preparing the recombinant porcine epidemic diarrhea virus S protein prepared in (2) into a water phase; (4) emulsifying the water phase and the ISA 201 VG adjuvant in a volume ratio of 46:54 to obtain a vaccine. The vaccine is high in safety, good in immunogenicity, stable in batches, low in production cost and strong in immunogenicity.

Abstract: Methods for passive transfer of immunity using recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such.

Abstract: Provided herein are, inter alia, methods of identifying agents that are capable inhibiting the binding (e.g., coupling) between a ROR1 protein and a ROR2 protein. By interfering with ROR1-ROR2 coupling (binding) the agents identified using the methods provided herein inhibit non-canonical Wnt5a signaling. Thus, the agents identified by the methods provided herein may, inter alia, be useful for cancer diagnosis and therapy.

Abstract: Improved anti-HPV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HPV39 E6E7 and HPV45 E6E7. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HPV are disclosed.

Abstract: The present invention relates to the field of (vector) vaccines, and especially to a canine distemper virus (CDV) vector comprising a heterologous nucleotide sequence which encodes a porcine epidemic diarrhea virus (PEDV) antigen. Said PEDV antigen is preferably a PEDV spike (S) protein. The viral vector of the present invention is useful for producing an immunogenic composition or vaccine for intranasally immunizing sows, and thereby protecting piglets, suckled by said sows, against the clinical signs associated with a PEDV infection.

Abstract: The present invention provides compositions and methods related to equine live-attenuated influenza vaccines.

Abstract: The present invention provides, among other things, a novel and improved method for generating “mosaic” influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered influenza B hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple influenza B viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.

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: This invention relates to the use of an agent capable of inhibiting IL-36 proteolytic processing for the treatment and/or reduction of inflammation in a subject. Advantageously, the agent prevents the production of a biologically active IL-36 to prevent and/or reduce the pro-inflammatory effects of IL-36. The invention also relates to a method for treatment and/or reduction of inflammation and compositions for treating and/or reducing inflammation.

Abstract: Disclosed herein are recombinant baculoviruses suitable for detecting the presence of arthropod-borne viruses in a biological sample of a test subject. The information derived from the detection may also be used to render a diagnosis on whether the test subject is infected with the arthropod-borne viruses or not, so that proper course of treatment may be assigned to the subject.

Abstract: Disclosed are recombinant chimeric influenza virus vaccines and live attenuated influenza virus (LAIV) vaccines expressing foreign (RSV) neutralizing epitopes or conserved M2e epitopes that are capable of providing broader cross-protection against influenza virus and/or protecting against respiratory syncytial virus (RSV) without vaccine-enhanced RSV disease (ERD).

Abstract: Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

Abstract: The present invention relates to canine influenza virus strains, and vaccines and compositions. The present invention also relates to reagents and methods allowing their detection, methods of vaccination as well as methods of producing these reagents and vaccines.

Abstract: The invention relates to methods of treating an EBV-LPD (Epstein-Barr Virus-associated lymphoproliferative disorder) in a human patient who has failed combination chemotherapy to treat the EBV-LPD and/or radiation therapy to treat the EBV-LPD, comprising administering to the human patient a population of allogeneic T cells comprising EBV-specific T cells.

Abstract: The present invention provides for functional chimeric gene regulatory units capable of driving strong and sustained heterologous gene expression.

Abstract: Engineered fusion proteins comprising a self-excising degron for controlling protein production are disclosed. In particular, the inventors have constructed fusion proteins comprising a degron connected to a protein of interest through a cleavable linker comprising a hepatitis C virus (HCV) protease site. The degron can be removed from the protein of interest by a czs-encoded HCV protease such that the protein of interest can be produced with minimal structural modification. Clinically available HCV protease inhibitors can be used to block protease cleavage such that the degron is retained after inhibitor addition on subsequently synthesized protein copies. The degron when attached causes rapid degradation of the linked protein. Such fusions of a degron to a protein of interest will be especially useful when control over protein production with minimal structural modification is desired.

Abstract: The invention relates to the field of virology. The invention provides an isolated essentially mammalian negative-sense single-stranded RNA virus (MPV) within the subfamily Pneumovirinae of the family Paramyxoviridae and identifiable as phylogenetically corresponding to the genus Metapneumovirus and components thereof.

Abstract: The present invention provides an antigen chimera, comprising: a fusion protein of an antigen and a mucosal immune adjuvant protein monomer capable of forming a multimer; and the mucosal immune adjuvant protein monomer capable of forming the multimer; wherein the mucosal immune adjuvant protein monomer capable of forming the multimer is one selected from cholera toxin B subunit (CTB) and E. coli heat-labile enterotoxin B subunit (LTB), the multimer is a pentamer, and in the chimera the molar ratio between the fusion protein and the mucosal immune adjuvant protein monomer capable of forming multimers is 1:4. In the present invention, a characteristic that a mucosal immune adjuvant protein can form a pentamer is used to form a chimeric structure, so as to form an antigen having a higher potency. Moreover, a mucosal immune adjuvant protein is used to improve an immune effect, so as to improve an effect of enhancing antigen immunogenicity.

Abstract: The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (“O interface”); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (“L domain”); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (“M domain”), as well as membrane-enveloped versions of the multimeric assemblies.

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

Abstract: Provided herein are optimized, recombinant influenza HA polypeptides that elicit immune responses. Also provided are compositions and kits comprising the optimized HA polypeptides as well as methods of making and using the optimized HA polypeptides.

Abstract: This invention provides vaccines comprising two or more recombinant Herpes Simplex Virus (HSV) proteins selected from a gD protein, a gC protein and a gE protein; and methods of impeding immune evasion by HSV thereby vaccinating a subject against HSV and treating, suppressing, inhibiting, and/or reducing an incidence of an HSV infection or a symptom or manifestation thereof, comprising administration of a vaccine of the present invention.

Abstract: The present invention relates to compositions and methods for the treatment and prevention of canine influenza virus (CIV) and CIV-related pathology. The present invention is based in part upon the discovery that various mutations in segment 1 and segment 2 of the CIV genome, thereby encoding mutant PB2 and PB1 protein, render the virus to be temperature-sensitive.

Abstract: The present invention encompasses FCV vaccines or compositions. The vaccine or composition may be a vaccine or composition containing FCV antigens. The invention also encompasses recombinant vectors encoding and expressing FCV antigens, epitopes or immunogens which can be used to protect animals against FCV infection.