Abstract: Replicons of genotype 3 of hepatitis C virus (HCV) are provided. These replicons contains adaptive mutations giving rise to the HCV's capability to replicate in vitro. Methods of preparing genotype 3 replicons and methods of using these replicons to screen antiviral agents are also provided.

Abstract: Methods and compositions concerning mutant flaviviruses with host-range phenotypes are provided. Nucleotide sequences that encode mutant flavivirus proteins are also provided. In certain aspects, viruses comprising these sequences display reduced replication in mammalian cells. In further aspects of the invention, flavivirus vaccine compositions and methods for vaccination against flavivirus infection are provided.

Abstract: Described herein is the development of a computationally optimized influenza HA protein that elicits broadly reactive immune response to all H5N1 influenza virus isolates. The optimized HA protein was developed through a series of HA protein alignments, and subsequent generation of consensus sequences, for clade 2 H5N1 influenza virus isolates. The final consensus HA amino acid sequence was reverse translated and optimized for expression in mammalian cells. Influenza virus-like particles containing the optimized HA protein are an effective vaccine against H5N1 influenza virus infection in animals.

Abstract: Provided herein are chimeric influenza hemagglutinin (HA) polypeptides, compositions comprising the same, vaccines comprising the same, and methods of their use.

Abstract: The inventors have successfully developed a recombinant vesicular stomatitis virus which expresses the major capsid protein of human norovirus. Infection of mammalian cells with the recombinant vesicular stomatitis virus resulted in production of high level of human norovirus virus-like particles. Importantly, the inventors further demonstrated that recombinant vesicular stomatitis virus expressing the major capsid protein of human norovirus displayed attenuated virulence in mice and elicited a high level of human norovirus-specific humoral, cellular, and mucosal immune responses in mice model. Therefore, norovirus-immunogenic compositions are herein provided, as are materials and methods useful to make and use the compositions.

Abstract: The present invention discloses a codon-optimized gene encoding major capsid protein L1 of human papilloma virus, which is capable, after transduced into a yeast cell, of efficiently expressing the major capsid protein L1 of human papilloma virus. The present invention also discloses an immunogenic macromolecule which is essentially produced by expression of said codon-optimized gene encoding the major capsid protein L1 of human papilloma virus in a yeast cell. The present invention further discloses the use of said immunogenic macromolecule and a composition comprising said immunogenic macromolecule.

Abstract: The present invention provides compositions comprising a vector including a nucleic acid comprising a nucleotide sequence encoding a peptide having the sequence X1LYQYMDDV, wherein X1 is any hydrophobic amino acid. The compositions are used to induce an immune response against human immunodeficiency virus (HIV).

Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

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 said EB-VLPs, a method of manufacturing a vaccine thereof, a vaccine and a composition comprising said EB-VLPs.

Abstract: A viral or non-viral vector particle having a modified viral surface protein wherein the viral surface protein is modified to include a targeting polypeptide including a binding region which binds to an extracellular matrix component. Such vector particles are useful in delivering genes encoding therapeutic agents to cells located at the site of an exposed extracellular matrix component.

Abstract: This document provides methods and materials for producing immune responses against hepatitis B viruses. For example, polypeptides, nucleic acid molecules encoding such polypeptides, virus-like particles containing such polypeptides, vaccine preparations containing one or more polypeptides provided herein, vaccine preparations containing one or more nucleic acid molecules provided herein, vaccine preparations containing one or more virus-like particles provided herein, and methods for inducing immune responses against hepatitis B viruses within mammals (e.g., humans) are provided.

Abstract: The present invention relates to compositions comprising replication defective Schmallenberg virus vaccines, methods of producing the vaccines, and the administration of such vaccines to animals, including ovines and bovines. The invention further relates to methods for providing long-term protective immunity against Schmallenberg in animals, including ovines and bovines.

Abstract: The present invention belongs to the field of animal health and relates to a nucleic acid sequence which comprises the genome of an infectious genotype I (EU) PRRS virus clone useful for studying Porcine Reproductive and Respiratory Syndrome (PRRS), a viral disease affecting swine, and in the development of vaccines, therapeutics and diagnostics for the prophylaxis, treatment and diagnosis of PRRS.

Abstract: The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

Abstract: The invention relates to a method for purifying compositions containing virus-like particles (VLP), wherein a VLP-containing composition is filtered through a filter medium, in particular through a membrane, having a molecular weight cut off (MWCO) of more than 30 kDa, and the cell culture supernatant of VLP-expressing cells is used as a VLP-containing composition. The invention further relates to a VLP-containing composition which can be produced by this method.

Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: Influenza virus-like particles (VLPs) comprising the structural proteins HA, NA, M1 and M2 are described. VLPs are also generated containing M1 alone, as are VLPs with M1 and any one or two of HA, NA and M2. VLPs with HA from one influenza subtype and NA from a different influenza subtype are also described, as are VLPs in which a portion or all of HA or NA is replaced by a heterologous moiety not produced by influenza virus, so as to comprise chimeric VLPs.

Abstract: A nucleic acid includes the 5? untranslated region, a virus protein-coding region including the NS3 protein coding sequence, the NS4A protein coding sequence, the NS4B protein coding sequence, the NS5A protein coding sequence, and the NS5B protein coding sequence, and the 3? untranslated region of the HCV J6CF genome in that order from the 5? to 3? direction. The NS4A protein coding sequence has a mutation for substituting alanine at position 1680 with glutamic acid, as determined on the basis of the amino acid sequence of the precursor protein of the J6CF strain.

Abstract: The application provides products, which may trigger pro-apoptotic or pro-death effects on neoplastic cells and/or tissues of the human nervous system, more particularly on neoplastic cells and/or tissues of the human CNS. The products of the application can be used as anti-proliferative or tumoricid agents in the treatment and/or palliation and/or prevention of neoplasms of the human nervous system, more particularly of glioblastoma or brain stem glioma. Therefore, the application also relates to compositions, such as pharmaceutical compositions or drugs, which comprise at least one of said products, as well as to the biotechnological and medical applications of said products and compositions.

Abstract: The present invention provides compositions relating to viral capsomeres which comprise foreign immunogenic sequences for use in pharmaceutical compositions and methods of producing such compositions, and related isolated or purified protein and nucleic acid molecules, vectors, host cells, compositions, and methods of use to augment an immune response, immunise an animal and prophylactically or therapeutically treat a disease, disorder or condition. The viral capsomere may be derived from a polyomavirus and comprise an immunogen of interest at the N-terminus and further at the C-terminus and/or at one or more exposed loops of the capsomere.

Abstract: Polypeptides comprising various amino acid sequences derived from Haemophilus influenzae type b, including a number of lipoproteins. These can be used in the development of vaccines for preventing and/or treating bacterial meningitis. They may also be useful for diagnostic purposes, and as targets for antibiotics. Antibodies against the polypeptides are also disclosed, as are the coding nucleic acids.

Abstract: Provided are live attenuated influenza A and B viruses as well as a composition, influenza A and B genes, a vector with a respective gene, a host cell comprising such vector, a method for preparing a live attenuated influenza A or B virus and a use of the influenza viruses as a vaccine. An influenza A virus contains a NP-gene, which includes a silent mutation at one or more positions selected from nucleotide 1467, nucleotide 1473, nucleotide 1500, nucleotide 1503, nucleotide 1512, nucleotide 1515, nucleotide 1518, nucleotide 1521, and nucleotide 1524 of SEQ ID No: 1. A PA gene includes a silent mutation at one or more positions corresponding to a position selected from nucleotides 2100 and 2103 of SEQ ID No: 3.

Abstract: The invention features stabilized human immunodeficiency virus (HIV) envelope (Env) trimers. The invention also features vaccines, nucleic acids, and vectors to deliver and/or facilitate production of the stabilized HIV Env trimers. In addition, the invention features methods of making and using the stabilized HIV Env trimers of the invention.

Abstract: Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.

Abstract: The present invention relates to a novel tail spike protein (TSP) encoded by the novel Listeria bacteriophage designated ProCC P825 and uses of the novel TSP for identifying, detecting and monitoring of Listeria.

Abstract: A subgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and a fullgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and infectious HCV particle-producing ability, each derived from a novel HCV of genotype 1b, are provided. Particularly, a subgenomic replicon RNA (nucleic acid) and a fullgenomic replicon RNA (nucleic acid), each derived from an HCV genome of the NC1 strain which is a novel HCV genotype 1b isolated from a patient with acute severe hepatitis C, are 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: The invention relates to building a chimeric polypeptide used for preventing or treating a Flaviviridae infection. The use of the inventive chimeric polypeptide for producing recombinant viral vectors such as a measles living viral vector is also disclosed.

Abstract: Consensus CHIKV E1 protein, consensus CHIKV E2 protein, consensus CHIKV capsid protein, or fragments and homologues thereof, and nucleic acid molecules that encode the same are disclosed. A consensus CHIKV Env protein which includes CHIKV E1 consensus protein, CHIKV E2 consensus protein, CHIKV E3 consensus protein, or fragments and homologues thereof and nucleic acid molecules that encode the same are also disclosed. Compositions and recombinant vaccines comprising CHIKV consensus proteins, and methods of using them are disclosed.

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: The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Abstract: The present invention relates to novel bacteriophages specific to Klebsiella pneumoniae strains, and compositions comprising the same. Particularly, polypeptides and their coding nucleic acid molecule of the novel bacteriophages are provided. The invention also relates to applications of the novel bacteriophages and the polypeptides in the detection/treatment/prevention of infection caused by Klebsiella pneumoniae strains. Development of immunogen and vaccine on the basis of the polypeptides are also provided.

Abstract: The present invention relates to attenuated, immunogenic West Nile virus chimeras built on a dengue virus backbone for the production of immunogenic, live, attenuated West Nile virus vaccines.

Abstract: The present inventors used the previously developed H77/JFH 1T27OOC,A4O8OT (1a/2a), J4/JFH 1T2996C,A4827T,?HVRI (1b/2a), J6/JFH 1?HVRI (2a/2a), J8/JFH 1?HVRI (2b/2a), S52/JFH 1T27i8G,?7i6oc (3a/2a), SA13/JFH 1C34O5G,A3696G (5a/2a) and HK6a/JFH 1T1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH 1 (genotype 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis of the viruses identified mutations adapting H77/JFH 1T27OOC,A4O8OT,?HVR1 (1a/2a), J8/JFH 1?HVR1 (2b/2a), S52/JFH 1T2718G,T716OC,?HVR1 (3a/2a) and J4/JFH 1T2996C,A4827T,?HVR1 (1b/2a) to the HVR1 deletion.

Abstract: The invention provides for mosaic influenza virus HA and NA sequences and uses thereof.

Abstract: The present invention is directed to novel nucleotide and amino acid sequences of Torque teno virus (“TTV”), including novel genotypes thereof, all of which are useful in the preparation of vaccines for treating and preventing diseases in swine and other animals. Vaccines provided according to the practice of the invention are effective against multiple swine TTV genotypes and isolates. Diagnostic and therapeutic polyclonal and monoclonal antibodies are also a feature of the present invention, as are infectious clones useful in the propagation of the virus and in the preparation of vaccines. Particularly important aspects of the invention include polynucleotide constructs that replicate in tissue culture and in host swine. The invention also provides for novel full length TTV genomes that can replicate efficiently in host animals and tissue culture.

Abstract: An isolated polynucleotide encoding an influenza multi-epitope polypeptide, wherein the multi-epitope polypeptide comprises multiple copies of a plurality of influenza virus peptide epitopes wherein the polypeptide is B(X1ZX2Z . . . Xm)nB or B(X1)nZ(X2)nZ . . . (Xm)nB; wherein B is an optional sequence of 1-4 amino acid residues; n is at each occurrence independently an integer of 2-50; m is an integer of 3-15; each of X1, X2 . . . Xm is an influenza peptide epitope of 4-24 amino acid residues; and Z at each occurrence is a bond or a spacer of 1-4 amino acid residues.

Abstract: Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus.

Abstract: A nucleic acid includes, in the following order, a 5? untranslated region comprising a particular nucleotide sequence of the genome of hepatitis C virus genotype 3a; a nucleotide sequence encoding a particular amino acid sequence of an NS3 protein, a nucleotide sequence encoding a particular amino acid sequence of an NS4A protein, a nucleotide sequence encoding a particular amino acid sequence of an NS4B protein, a nucleotide sequence encoding a particular amino acid sequence of an NS5A protein, a nucleotide sequence encoding a particular amino acid sequence of an NS5B protein of the hepatitis C virus genotype 3a; and a 3? untranslated region comprising a particular nucleotide sequence of a genome of hepatitis C virus genotype 3a.

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: The present disclosure provides a DNA molecule capable of replication in Mycobacteria having a nucleic acid sequence as disclosed in SEQ ID NO: 1, a shuttle vector constructed using it and a transformed cells containing the present vector. The vector of about 18 kb of the present disclosure contains 16 ORFs, a replication origin and a rep-like protein essential for replication. Therefore, the plasmid of the present disclosure can be utilized as a gene delivery system/research, and also in a therapeutic system such as immune therapeutics by effectively delivering proteins or heterologous DNA and expressing the encoded DNA in cells.

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: Provided is an isolated mammalian negative strand RNA virus, metapneumovirus (MPV), within the sub-family Pneumoviridae, of the family Paramyxoviridae. Also provided are isolated mammalian negative strand RNA viruses identifiable as phylogenetically corresponding or relating to the genus Metapneumovirus and components thereof. In particular, provided is a mammalian MPV, subgroups and variants thereof. Also provided are genomic nucleotide sequences of different isolates of mammalian MPV, in particular, human MPV. Disclosed is the use of the sequence information of different isolates of mammalian MPV for diagnostic and therapeutic methods. Provided are nucleotide sequences encoding the genome of a MPV or a portion thereof, including both mammalian and avian MPV. Further described are chimeric or recombinant viruses encoded by the nucleotide sequences, and chimeric and recombinant mammalian MPV that comprise one or more non-native or heterologous sequences.

Abstract: This document provides methods and materials related to vesicular stomatitis viruses containing a G polypeptide of a maraba virus. For example, vesicular stomatitis viruses containing a G polypeptide of a maraba virus (e.g., pseudotyped viruses), nucleic acid molecules encoding vesicular stomatitis viruses containing a G polypeptide of a maraba virus, methods for making vesicular stomatitis viruses containing a G polypeptide of a maraba virus, and methods for using vesicular stomatitis viruses containing a G polypeptide of a maraba virus to treat cancer or infectious diseases are provided.

Abstract: Disclosed are immunogens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the immunogens and methods of producing the immunogens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the immunogen to the subject.

Abstract: The present invention provides methods and compositions comprising a chimeric norovirus capsid protein comprising a norovirus VP1 major capsid protein backbone comprising a norovirus epitope selected from the group consisting of: a) Epitope A; b) Epitope B; c) Epitope C; d) Epitope D; e) Epitope E; f) Epitope F; and g) any combination of (a) through (f) above, wherein the norovirus epitope is from a norovirus strain that is different from the norovirus VP1 major capsid protein backbone.

Abstract: The present invention relates to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) mutant strains having increased stability; compositions containing the strains or antigens derived therefrom; vaccines containing the strains, including killed, attenuated or subunit vaccines; nucleic acids encoding PRRSV polypeptides, polypeptides encoded by the nucleic acids, including antigenic fragments thereof; antibodies which specifically bind to said polypeptides, and methods making and using thereof.

Abstract: Provided herein are methods for determining the susceptibility of a hepatitis C virus (HCV) in a patient to anti-viral agents, particularly cyclophilin inhibitors such as cyclosporine A. More particularly, provided herein are methods for determining the amino acid sequence within a region of the HCV NS5A protein and comparing the viral amino acid sequence to that of a reference strain, wherein the existence of at least one variation in the viral genome is indicative that the virus is more or less susceptible to anti-viral agents relative to the reference strain. Also provided are isolated polynucleotide molecules, replicons, and kits that can be used to assay the susceptibility of a particular HCV to an anti-viral agent.

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.