Abstract: Improved anti-HCV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HCV genotype 1 a/1 b NS3 and NS4A. Pharmaceutical composition, recombinant vaccines comprising and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HCV are disclosed.

Abstract: The present invention provides methods of immunizing a subject against a tumor, inhibiting tumor growth, inhibiting tumor recurrence, treating, suppressing the growth of, or decreasing the incidence of a tumor, overcoming tolerance to a tumor vasculature marker (TVM) in a subject comprising the step of administering a vaccine comprising a TVM or a nucleic acid encoding a TVM and related vaccines. The present invention also provides a method of targeting a tumor vasculature in a subject having a tumor comprising the step of contacting said subject with a labeled compound that binds a) a tumor vasculature marker (TVM) or b) a nucleic acid molecule encoding said TVM.

Abstract: Disclosed is a recombinant nonpermutated bacteriophage that includes a nucleic acid sequence that is at least 150 kb in length wherein the bacteriophage is made to display one or more surface antigens such as heterologous polypeptides, and compositions and kits that include the recombinant nonpermutated bacteriophages of the present invention. Also disclosed are methods of inducing an immune response in a subject that involve administration of a pharmaceutically effective amount of a composition comprising the recombinant nonpermutated bacteriophages of the present invention.

Abstract: The present invention relates to recombinant parapoxviruses comprising heterologous DNA derived from a canine distemper virus, to the preparation of such constructs, and to their use in immunogenic compositions and vaccines. It further relates to the use of recombinant parapoxviruses for diagnostics.

Abstract: The present invention relates to a replication deficient recombinant virus encoding at least one antigen and/or antigenic epitope, wherein expression of said antigen and/or antigenic epitope is regulated by a transcriptional control element comprising at least two elements driving early expression of said antigen and/or antigenic epitope and the use of said replication deficient recombinant virus as medicament or vaccine.

Abstract: The invention relates to novel insertion sites useful for the integration of HIV DNA sequences into the MVA genome, and to the resulting recombinant MVA derivatives.

Abstract: Recombinant viral vectors, especially parvovirus vectors such as adeno-associated virus (AAV) vectors; capable of enhanced expression of heterologous sequences, and methods for their construction and use, are provided. The vectors have a structure, or are capable of rapidly adopting a structure, which involves intrastrand base pairing of at least one region in a heterologous sequence.

Abstract: The present invention relates, in general, to a methodology for the generation of nonsegmented negative-strand RNA viruses (Pringle, 1991) from cloned deoxyribonucleic acid (cDNA). Such rescued viruses are suitable for use as vaccines, or alternatively, as plasmids in somatic gene therapy applications. The invention also relates to cDNA molecules suitable as tools in this methodology and to helper cell lines allowing the direct rescue of such viruses. Measles virus (MV) is used as a mode for other representatives of the Mononegavirales, in particular the family Paramyxoviridae.

Abstract: Vaccines comprising one or more recombinant raccoon pox viruses and methods of using those vaccines to immunize avians.

Abstract: The invention provides chimeric flavivirus vaccines against West Nile virus and methods of using these vaccines to prevent or treat West Nile virus infection.

Abstract: This invention provides flavivirus vaccines that comprise live-attenuated flaviviruses and methods of making and using these vaccines. The flavivirus vaccines described herein possess higher potency due to in situ production of additional immunogens in a way that mimics viral infection and the vaccines have potential for higher potency, reducing costs for production and delivery.

Abstract: Described are new uses of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, also described are new assays to determine the best regimen for applying the most suitable recombinant viral vector in a vaccination or gene therapy setting.

Abstract: A vaccine is described, comprising an inactivated viral vector having inserted an exogenous nucleotide sequence coding for a disease of concern; and, a pharmaceutically acceptable vehicle, adjuvant or excipient, which provides due protection against the disease of concern by using a viral vector titer similar to that required for an active-virus vaccine based on the same viral vector. Mainly, viral vectors of paramixovirus or adenovirus are described.

Abstract: An aspect of the present invention is directed towards DNA plasmid vaccines capable of generating in a mammal an immune response against a plurality of influenza virus subtypes, comprising a DNA plasmid and a pharmaceutically acceptable excipient. The DNA plasmid is capable of expressing a consensus influenza antigen in a cell of the mammal in a quantity effective to elicit an immune response in the mammal, wherein the consensus influenza antigen comprises consensus hemagglutinin (HA), neuraminidase (NA), matrix protein, nucleoprotein, M2 ectodomain-nucleo-protein (M2e-NP), or a combination thereof. Preferably the consensus influenza antigen comprises HA, NA, M2e-NP, or a combination thereof. The DNA plasmid comprises a promoter operably linked to a coding sequence that encodes the consensus influenza antigen. Additionally, an aspect of the present invention includes methods of eliciting an immune response against a plurality of influenza virus subtypes in a mammal using the DNA plasmid vaccines provided.

Abstract: The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining LNs, where it can potently activate Foxp3 regulatory T cells (Tregs). We now show that IDO functions as a molecular switch in tumor-draining LNs, maintaining Tregs in their normal suppressive phenotype when IDO was active, but allowing inflammation-induced conversion of Tregs to a polyfunctional T-helper phenotype similar to proinflammatory TH17 cells when IDO was blocked. In vitro, conversion of Tregs to the TH17-like phenotype was driven by antigen-activated effector T cells, and required IL-6 produced by activated pDCs. IDO regulated this conversion by dominantly suppressing production of IL-6 in pDCs, in a GCN2-kinase dependent fashion.

Abstract: The invention relates to a dengue virus tetravalent vaccine containing a common 30 nucleotide deletion (?30) in the 3?-untranslated region of the genome of dengue virus serotypes 1, 2, 3, and 4, or antigenic chimeric dengue viruses of serotypes 1, 2, 3, and 4.

Abstract: Therapeutic methods and microorganisms therefor are provided. The microorganisms are designed to accumulate in immunoprivileged tissues and cells, such as in tumors and other proliferating tissue and in inflamed tissues, compared to other tissues, cells and organs, so that they exhibit relatively low toxicity to host organisms. The microorganisms also are designed or modified to result in leaky cell membranes of cells in which they accumulate, resulting in production of antibodies reactive against proteins and other cellular products and also permitting exploitation of proferating proliferating tissues, particularly tumors, to produce selected proteins and other products. Vaccines containing the microorganisms are provided. Combinations of the microorganisms and anti-cancer agents and uses thereof for treating cancer also are provided.

Abstract: Aspects of the present invention relate to chimeric polypeptides including HCV NS3/4A sequences and T-cell epitopes. Embodiments include nucleic acids encoding the chimeric NS3/4A polypeptides, the encoded polypeptides, compositions containing said nucleic acids, compositions containing said chimeric polypeptides, as well as methods of making and using the aforementioned compositions including, but not limited to medicaments and vaccines.

Abstract: The invention relates to recombinant MVA which is capable of expressing structural HCV antigens, functional parts of said structural antigens or epitopes of said structural antigens. The invention further relates to a pharmaceutical composition, especially in the form of a vaccine and containing the recombinant MVA according to the invention, to eukaryotic cells that contain the inventive recombinant MVA and to various uses of the recombinant MVA, for example for producing recombinant structural proteins, for producing a pharmaceutical preparation that is suitable for the therapy and prophylaxis of HCV infections and diseases thereby caused. The invention further relates to methods for producing recombinant MVA and recombinant structural HCV polypeptides encoded by said recombinant MVA, and to DNA or RNA of said recombinant MVA.

Abstract: The invention relates to a porcine adenovirus 3 based vaccine for the treatment of PRRS virus infection where the PADV3 is a recombinant replication competent PADV3 that comprises a nucleic acid that encodes a novel fusion protein of PRRSV ORF6 and a modified PRRSV ORF5 either alone or in combination with a PRRSV ORF.

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: The present invention refers to a recombinant koi herpesvirus (KHV) or Cyprinid herpesvirus 3 (CyHV-3), which is immunogenic in fish, preferably in carps, more preferably in Cyprinus carpio, and to a vaccine for preventive and/or therapeutic treatment of a disease caused by koi herpesvirus (KHV) or CyHV-3. The 5 recombinant herpesvirus is used to confer immunity on fish, preferably on carps, more preferably on Cyprinus carpio, against a disease caused by koi herpesvirus (KHV) or Cyprinid herpesvirus 3 (CyHV-3).

Abstract: The present invention relates to recombinant parapoxviruses which carry in their genomes comprising heterologous DNA derived from a rabies virus, to the preparation of such constructs, and to their use in immunogenic compositions and vaccines. It further relates to the use of recombinant parapoxviruses for diagnostics.

Abstract: Attenuated, replication-deficient viruses such as vaccinia viruses are used to deliver an exogenous viral, bacterial, parasitic or tumor antigen to an epidermal tissue such as the skin, lungs or gastrointestinal tract, which has been mechanically disrupted, in an amount effective to elicit or stimulate a cell mediated immune response. The epidermal tissue may be mechanically disrupted by a device such as a scarification needle or an abrader device. The epidermis may be mechanically disrupted prior to, at the same time, or immediately after the administration of the vaccine. The vaccine can be used to induce immunity against a pathogen, such as a virus, bacteria, or parasite, or against a cancer in a subject that has or is at risk of developing cancer. In some embodiments a co-stimulatory molecule, a growth factor, an adjuvant and/or a cytokine is administered before, with or after the viral vaccine. In some embodiments, the co-stimulatory molecule is co-expressed with the antigen by the virus.

Abstract: The present invention provides a DNA vaccine for carps for inducing protective immunity against Koi herpesvirus (KHV). The DNA vaccine comprises a DNA comprising a nucleotide sequence encoding an immunogenic polypeptide against Koi herpesvirus (KHV) of carps, or an expression vector comprising the DNA as an active ingredient.

Abstract: The present invention discloses the construction of dengue virus subgenomic replicons containing large deletions in the structural region (C-preM-E) of the genome, which replicons are useful as vaccines to protect against dengue virus infection.

Abstract: The invention provides polynucleotides and polypeptides encoded therefrom that are capable of inducing immune responses to a human immunodeficiency virus. Compositions and methods for utilizing polynucleotides and polypeptides of the invention are also provided.

Abstract: An attenuated rabies virus for use as a vaccine. The attenuated rabies virus expresses an immune factor that enhances immune response upon administration of the vaccine.

Abstract: Screening and diagnostic reagents, kits and methods for metastatic colorectal cancer or primary and/or metastatic stomach or esophageal cancer are disclosed. Vaccines compositions and methods of for treating and preventing metastatic colorectal cancer or primary and/or metastatic stomach or esophageal cancer are disclosed.

Abstract: The present invention relates to novel insertion sites useful for the integration of exogenous sequences into the Modified Vaccinia Ankara (MVA) virus genome. The present invention further provides plasmid vectors to insert exogenous DNA into the genome of MVA. Furthermore, the present invention provides recombinant MVA comprising an exogenous DNA sequence inserted into the new insertion site as medicine or vaccine.

Abstract: The invention relates to an attenuated non-segmented negative-sense RNA virus characterized by at least one mutation in the L gene wherein the mutation reduces viral replication, the methods of manufacturing and methods of use.

Abstract: This invention relates to the identification of prostate stem cell antigen (PSCA) as a target of clinically relevant antitumor immune responses. The invention provides vaccines comprising PSCA, or fragments thereof, which are useful in inducing antitumor immune responses, including PSCA specific CD8+ T cell responses. Methods of using the compositions to treat cancer are also provided. The invention further provides methods of identifying compounds useful in antitumor vaccines and methods of assessing the responses of patients to cancer immunotherapy.

Abstract: This invention provides a new approach to the design of a virus with a defective replication cycle, which can be rescued by wild type virus co-infection, and which expresses foreign antigenic epitopes that contribute to the elimination of virus infected cells and then to viral clearance. The vector of the invention, by expression of epitopes derived from common pathogens, by-passes existing tolerance of virus specific T cell responses. The vector will only replicate in virus infected cells.

Abstract: The invention relates to novel insertion sites useful for the integration of HIV DNA sequences into the MVA genome, and to the resulting recombinant MVA derivatives.

Abstract: The invention provides attenuated Flavivirus vaccines, such as vaccines against Japanese encephalitis virus and West Nile virus, as well as methods of making and using these vaccines.

Abstract: The present invention encompasses FMDV vaccines or compositions. The vaccine or composition may be a vaccine or composition containing FMDV antigens. The invention also encompasses recombinant vectors encoding and expressing FMDV antigens, epitopes or immunogens which can be used to protect animals, in particular ovines, bovines, caprines, or porcines, against FMDV.

Abstract: The invention provides a vaccine comprising an effective amount of an isolated recombinant influenza virus comprising a mutant M gene segment that is mutated so that upon viral replication the mutant M gene expresses a functional M1 protein and a mutant M2 protein with a deletion of the cytoplasmic tail and either lacking a transmembrane domain or having a mutated transmembrane domain.

Abstract: The present invention relates, inter alia, to a method of raising an immune response against a pathogen which comprises administering (i) one or more first immunogenic polypeptides derived from said pathogen; (ii) one or more viral vectors comprising one or more heterologous polynucleotides encoding one or more second immunogenic polypeptides derived from said pathogen; and (iii) an adjuvant; wherein the one or more first immunogenic polypeptides, the one or more viral vectors and the adjuvant are administered concomitantly. The invention also relates to vaccines, pharmaceutical compositions, kits and uses employing said polypeptides, viral vectors and adjuvants.

Abstract: The present invention relates to an avirulent, oncolytic herpes simplex virus modified from a wild-type herpes simplex virus so that both ?134.5 genes of the virus have been deleted and each replaced with an interferon-resistance gene that is expressed as an immediate-early gene. The present invention also relates to a pharmaceutical composition that includes the modified herpes simplex virus of the present invention and a pharmaceutically acceptable vehicle for in situ administration to tumor cells. Also provided in the present invention are methods for killing tumor cells in a subject and for immunizing a subject against an infectious disease, cancer, or an autoimmune disease that involve administering to a subject the modified avirulent, oncolytic herpes simplex virus of the present invention.

Abstract: A vaccine comprising an immunogenic preparation containing a plasmodium antigen or a fragment thereof, wherein said antigen is selected from a group consisting of PyAg2, PfAg2, PvAg2, PkAg2, PoAg2, PmAg2, PbAg2, PcAg2 and a combination thereof. A vaccination method comprising administering a priming immunization preparation containing a plasmodium antigen or fragment thereof, wherein said antigen is selected from a group consisting of PyAg2, PfAg2, PvAg2, PkAg2, PoAg2, PmAg2, PbAg2, PcAg2 and a combination thereof, and administrating a boosting immunization preparation containing said plasmodium antigen or fragment, wherein said antigen is selected from a group consisting of PyAg2, PfAg2, PvAg2, PkAg2, PoAg2, PmAg2, PbAg2, PcAg2 and a combination thereof. The vaccination method further comprising co-administration of an immune modulating drug.

Abstract: The invention relates to novel insertion sites useful for the integration of HIV DNA sequences into the MVA genome, and to the resulting recombinant MVA derivatives.

Abstract: Methods for production of tumor-specific antibodies are provided. The methods employ microorganisms that are designed to accumulate in immunoprivileged tissues and cells, such as in tumors and other proliferating tissue and in inflamed tissues, compared to other tissues, cells and organs, so that they exhibit relatively low toxicity to host organisms. The microorganisms also are designed or modified to result in leaky cell membranes of cells in which they accumulate, resulting in production of antibodies reactive against proteins and other cellular products and also permitting exploitation of proliferating tissues, particularly tumors, to produce selected proteins and other products.

Abstract: The present invention relates to genetic vaccines for stimulating cellular and humoral immune responses in humans and other hosts, and, in particular, relates to recombinant viruses that express heterologous antigens of pathogenic viruses, in single dose form.

Abstract: Methods and compositions concerning mutant flaviviruses with reduced virulence. In some embodiments the invention concerns nucleotide sequences that encode mutant flaviviral proteins. Viruses comprising mutant NS1 and NS4B genes display reduced virulence are provided. In further aspects of the invention, flavivirus vaccine compositions such as West Nile virus vaccines are provided. In another embodiment the invention provides methods for vaccination against flavivirus infection.

Abstract: An improved method of inducing and/or enhancing an immune response to a tumor antigen is disclosed. The method involves administering the tumor antigen, nucleic acid coding therefor, vectors and/or cells comprising said nucleic acid, or vaccines comprising the aforementioned to a lymphatic site.

Abstract: The compositions and methods of the invention described herein provide treatments against Ebola virus infection by expressing gene(s) from the Ivory Coast ebolavirus (ICEBOV) species in a recombinant viral vector.

Abstract: The present invention relates to methods for purification of Vaccinia viruses (W) and/or Vaccinia virus (W) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

Abstract: The present invention relates to the engineering of recombinant influenza viruses that express tumor-associated antigens. Expression of tumor-associated antigens by these viruses can be achieved by engineering specific epitopes into influenza virus proteins, or by engineering viral genes that encode a viral protein and the specific antigen as independent polypeptides. Tumor-bearing patients can be immunized with the recombinant influenza viruses alone, or in combination with another treatment, to induce an immune response that leads to tumor reduction. The recombinant viruses can also be used to vaccinate high risk tumor-free patients to prevent tumor formation in vivo.

Abstract: Recombinant VSV viral particles and the use thereof as vaccines for immunization are described.

Abstract: The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. The invention also relates to the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. The invention furthermore relates to the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.