Abstract: The invention provides chimeric flavivirus vectors encoding one or more structural proteins from a first flavivirus with a low level of replication in a cell, such as dengue virus and yellow fever virus, and a backbone from a second flavivirus with a high level of replication in the cell, such as the Rio Bravo virus or the Uganda S virus. The chimeric flaviviruses encoded by the chimeric flavivirus vectors of the invention can be used to vaccinate subjects to prevent infection from infectious flaviviruses, including dengue viruses and yellow fever viruses.

Abstract: The present invention relates to recombinant bovine parainfluenza virus (bPIV) cDNA or RNA which may be used to express heterologous gene products in appropriate host cell systems and/or to rescue negative strand RNA recombinant viruses that express, package, and/or present the heterologous gene product. The chimeric viruses and expression products may advantageously be used in vaccine formulations including vaccines against a broad range of pathogens and antigens.

Abstract: The invention provides a new type of a capsid protein VP1 of human enterovirus 71, named as MEL701-VP1 and functional/structural variants thereof, which is used for protection against enterovirus. The transgenic animal producing the protein, the composition comprising the protein and the method for production thereof are also provided.

Abstract: The invention provides recombinant flavivirus vaccines that can be used in the prevention and treatment of flavivirus infection. The vaccines of the invention contain recombinant flaviviruses including attenuating mutations.

Abstract: This disclosure relates to methods of using recombinant replication-deficient cytomegalovirus (CMV) to generate a long-term, repeatedly stimulated T cell-based immune response in a subject, for instance against a heterologous antigen expressed by the cytomegalovirus. It further relates to methods of using a recombinant replication deficient CMV as an anti-cancer immunogenic preparation.

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 present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Abstract: The invention relates to methods of stimulating an immune response against an antigenic protein in a mammalian subject. More specifically, the invention relates to routes of administration of a hybrid Newcastle Disease Virus-vector (NDV-vector) for eliciting an immune response against an antigenic protein that is encoded by the hybrid NDV-vector.

Abstract: The invention provides a packaging (incorporation) signal for influenza virus vectors, and methods of using the signal to transmit and maintain influenza viral and foreign nucleic acid in virus and cells.

Abstract: Provided are expression vectors for generating an immune response to a mucin. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal, a mucin antigen and CD40 ligand. Also provided are methods of generating an immune response against cells expressing a mucin by administering an effective amount of the vector. Further provided are methods of generating an immune response against cancer cells expressing a mucin in an individual by administering an effective amount of the vector. Still further provided are methods of overcoming anergy to a mucin self antigen by administering an effective amount of the vector.

Abstract: The present invention relates to adjuvanted recombinant anti-rabies vaccines and the oral administration of such vaccines to raccoons and other wildlife. Advantageously, the anti-rabies vaccine may comprise a recombinant vaccinia virus containing a rabies glycoprotein gene. The invention encompasses methods of vaccinating raccoons and other wildlife by administration of an anti-rabies vaccines which may comprise a recombinant vaccinia virus containing a rabies glycoprotein gene, in combination with an adjuvant which increases both vaccine viscosity and efficacy. The invention provides effective oral recombinant vaccines used in oral rabies vaccination (ORV) programs for wildlife, effective at protecting raccoons, gray foxes, coyotes, and other animals.

Abstract: The invention relates to peptide compositions for use in the preparation of pharmaceutical compositions against hepatitis C virus, as well as corresponding methods.

Abstract: The immunogenicity of the influenza virus hemagglutinin (HA) molecule may be increased by substitutions of amino acids in the HA sequence. The substitution of specific HA residues, such as asparagine at position 223 of H5 HA, increase the sensitivity of the hemagglutinin inhibition (HI) assay by altering receptor specificity and/or antibody-antigen binding. HA molecules containing such substitutions will be useful in the development of diagnostic reference viruses and improved influenza vaccines.

Abstract: Provided herein is a vaccine which is safe and effective against Nipah virus infection and a vector which is used in the manufacture of this vaccine and to provide a bivalent vaccine which exhibits an excellent preventive effect against measles virus and Nipah virus infection and which eliminates complexity at the time of inoculation. Also provided is a recombinant measles virus in which is inserted a gene which encodes a protein involved in preventing Nipah infection into the measles virus genome. The protein involved in preventing Nipah virus infection is preferably G protein or F protein which is a membrane protein. Also provided is a bivalent vaccine against measles and Nipah virus infection which contains the recombinant measles virus.

Abstract: The present invention relates to recombinant modified vaccinia Ankara (MVA) virus containing restructured sites useful for the integration of heterologous nucleic acid sequences into an intergenic region (IGR) of the virus genome, where the IGR is located between two adjacent, essential open reading frames (ORFs) of the vaccinia virus genome, wherein the adjacent essential ORFs are non-adjacent in a parental MVA virus used to construct the recombinant MVA virus, and to related nucleic acid constructs useful for inserting heterologous DNA into the genome of a vaccinia virus, and further to the use of the disclosed viruses as a medicine or vaccine.

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 method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.

Abstract: The present invention broadly relates to the synergistic attenuation of vesicular stomatitis virus (VSV). More particularly, the invention relates to the identification of combined mutation classes which synergistically attenuate the pathogenicity of VSV vectors in mammals and immunogenic compositions thereof.

Abstract: The invention provides a recombinant rabies viruses comprising three copies of a mutated G gene wherein each G gene encodes a rabies virus glycoprotein having the amino acid 194 mutated to a serine and the amino acid 333 is mutated to a glutamic acid. The recombinant rabies virus is nonpathogenic in immunodeficient mammals and can be used in a vaccine to induce an immune response protect mammals from infection by rabies virus as well as clear a pre-existing rabies virus infection from neural tissues.

Abstract: The invention provides novel vaccination strategies based on a prime-boost vaccination regiment. The inventors have determined improved ways of boosting an immune response in a patient previously primed or exposed to a plurality of epitopes. The improved method requires the epitopes in the boosting phase to be administered individually, i.e. held on separate peptide constructs.

Abstract: Described herein are modified influenza virus NS gene segments and nucleic acid sequences encoding such modified influenza virus NS gene segments. In certain embodiments, a modified influenza virus NS gene segment described herein comprises an influenza virus NS 1 open reading frame (ORF) lacking a stop codon, a heterologous nucleotide sequence, a 2A autoproteolytic cleavage site or another cleavage site, an NEP ORF, wherein the gene segment has one or more mutations in either the splice acceptor site, splice donor site, or both the splice acceptor and splice donor sites that prevents splicing of mRNA. Also described herein are recombinant influenza viruses comprising a modified influenza virus NS gene segment and the use of such viruses. The recombinant influenza viruses may be use in the prevention and/or treatment of influenza virus disease or as a delivery vector.

Abstract: The present invention provides a composition comprising hepatitis B virus (HBV) component(s), and which may be either nucleic acid- or polypeptide-based as well as nucleic acid molecules and vectors encoding such HBV component(s). It also relates to infectious viral particles and host cells comprising such nucleic acid molecules or vectors. It also provides composition and kits of parts comprising such nucleic acid molecules, vectors, infectious viral particles or host cells and the therapeutic use thereof for preventing or treating HBV infections.

Abstract: The present invention relates to a method for inducing an immune response to the dengue virus, on the basis of DNA and 17D chimeric virus vaccines in combined or co-administered immunisation. The scope of the present invention also includes DNA vaccines against the four serotypes of the dengue virus, produced by forming, from each viral serotype of the dengue virus (DENV1-4), various recombinant plasmids that contain the gene that codes for the E protein, or that contain only the sequence that corresponds to the domain III of this protein. The invention also provides a vaccine composition consisting of (a) DNA vaccines against the four serotypes of the dengue virus; (b) chimeric viruses comprising the modified yellow fever vaccination virus 17D; and (c) a pharmaceutically acceptable carrier, all of which are covered by the scope of the invention.

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: Compositions, recombinant vaccines and live attenuated pathogens comprising one or more isolated nucleic acid molecules that encode an immunogen in combination with an isolated nucleic acid molecule that encodes IL-15Ra or a functional fragment thereof are disclosed. Methods of inducing an immune response in an individual against an immunogen, using such compositions are disclosed.

Abstract: A method of inducing an antigen-specific immune response in a mammalian subject includes the steps of administering to the subject an effective amount of a first composition comprising a DNA plasmid comprising a DNA sequence encoding an antigen under the control of regulatory sequences directing expression thereof in a mammalian or vertebrate cell. The method also includes administering to the subject an effective amount of a second composition comprising a recombinant vesicular stomatitis virus (rVSV) comprising a nucleic acid sequence encoding the antigen under the control of regulatory sequences directing expression thereof in the mammalian or vertebrate cell. The rVSV is in one embodiment replication competent. Kits for use in immunizations and therapeutic treatments of disease include the components and instructions for practice of this method.

Abstract: Methods for treating or preventing recurrence of hyper proliferating diseases, e.g., cancer, are described. A method may comprise priming a mammal by administering to the mammal an effective amount of a nucleic acid composition encoding an antigen or a biologically active homo log thereof and boosting the mammal by administering to the mammal an effective amount of an oncolytic virus comprising a nucleic acid encoding the antigen or the biologically active homolog thereof.

Abstract: The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus, wherein the MVA-BN virus, or a derivative thereof, induces at least substantially the same level of immunity in vaccinia virus prime/vaccina virus boost regimes when compared to DNA prime/vaccinia virus boost regimes. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus.

Abstract: The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus, wherein the MVA-BN virus, or a derivative thereof, induces at least substantially the same level of immunity in vaccinia virus prime/vaccina virus boost regimes when compared to DNA prime/vaccinia virus boost regimes. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus.

Abstract: The invention relates to methods and kits comprising poxviruses including, but not limited to modified vaccinia virus Ankara (MVA) and uses thereof to provide immediate protection against pathogens. Poxviruses including, but not limited to MVA can be delivered to a host animal just prior to or after exposure to a pathogen and provide protection against the pathogen.

Abstract: It is disclosed herein that Brachyury is expressed in human tumors, specifically in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, as well as in lung, colon and prostate carcinomas. Immunogenic Brachyury polypeptides are disclosed herein. These polypeptides can be used in diagnostic assays for Brachyury expression, as well as for inducing an immune response to Brachyury. Polynucleotides encoding the immunogenic Brachyury polypeptides, vectors including these polypeptides, host cells transformed with these vectors, and methods of using these polypeptides, polynucleotides, vectors, and host cells are provided. Methods of diagnosing a Brachyury-expressing cancer are also provided. Exemplary cancers include small lung, colon, intestine, stomach, kidney, bladder, uterus, ovary, and testes and prostate cancers. Methods of treating cancer are also disclosed.

Abstract: The present invention relates to the discovery of novel T cell epitopes of the human HER-2/Neu protein that is promiscuous for at least 25 different HLA-DR alleles. The invention also relates to compositions that contain one of the novel epitopes or a fusion peptide of such a epitope and a heterologous polypeptide. Further disclosed herein is the use of the epitopes or their fusion peptides, and compositions containing the epitopes or their fusion peptides.

Abstract: The immune response to an antigen of interest, either in purified form or expressed via an alphavirus replicon particle, can be enhanced by the simultaneous administration of an alphavirus replicon particle which expresses interleukin-12. This allows for the use of significantly smaller quantities of the antigen and this immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

Abstract: An antiviral vaccine that encodes costimulation molecules for increasing immune response to the particular virus at issue is provided herein. In an illustrative embodiment, in mice lacking both B7-1 and B7-2 (B7KO), the increased severity of HSV infection has confirmed the importance of these molecules in generation of HSV-specific immunity. To test the concept that B7-1 or B7-2 expression by replication-defective HSV could augment its immunogenicity and protective capacity, the present inventors constructed replication-defective HSV-2 encoding B7-1 or B7-2. Both viruses partially reconstituted immune responses to HSV compared with replication-defective virus alone when used to immunize B7KO mice, indicating that the increased responsiveness to virus could be attributed to virus-encoded B7 molecules.

Abstract: Disclosed is a intranasal spray-type tuberculosis vaccine, which has a high prophylactic effect on human tuberculosis, particularly adult tuberculosis. The nebulizable tuberculosis vaccine for intranasal administration comprises a paramyxovirus gene (particularly rhPIV2) having, integrated therein, a gene encoding an ? antigen derived from an acid-fast bacterium (e.g., an ? antigen derived from Mycobacterium kansasii or Mycobacterium bovis BCG), an analogue of the gene, or a variant of the gene which has an equivalent function to that of the gene.

Abstract: The immune response to an antigen of interest, either in purified form or expressed via an alphavirus replicon particle, can be enhanced by the simultaneous administration of an alphavirus replicon particle which expresses interleukin-12. This allows for the use of significantly smaller quantities of the antigen and this immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

Abstract: The present disclosure relates to adenovirus protein modifications to augment immune response to a transgene of a recombinant adenovirus and to circumvent pre-existing anti-adenovirus immunity. Some embodiments are directed to a recombinant adenovirus derived from a recombinant adenovirus plasmid vector, wherein the recombinant adenovirus plasmid vector comprises a nucleotide sequence encoding a Plasmodium circumsporozoite protein, or antigenic portion thereof, operably linked to a heterologous promoter and a modified capsid or core protein, wherein an immunogenic epitope of Plasmodium circumsporozoite is inserted into or replaces at least part of a capsid or core protein. Other embodiments are directed to a pharmaceutical composition or a malaria vaccine composition comprising a recombinant adenovirus according to the above embodiments.

Abstract: Nucleic acid molecules that encode IL-15 or fragments thereof, which express protein at a higher level than nucleic acid molecules with native coding sequences for IL-15 are disclosed. Nucleic acid molecules with additional modifications such as the absence of coding sequences for IL-15 signal sequences and/or the absence of IL-15 untranslated sequences and/or inclusion of non-IL-15 signal sequences are also disclosed. Vectors, including plasmids and viral vectors, comprising such nucleic acid molecules; and to host cells comprising such nucleic acid molecules are disclosed as well as methods of using such nucleic acid molecules alone or in combination with nucleic acid sequences encoding immunogens which are part of the nucleic acid molecules and/or part of a different nucleic acid molecule. Recombinant vaccines and live attenuated pathogens encoding fusion proteins, and methods of using the same, are disclosed.

Abstract: A liquid or liquid-frozen composition comprising: a modified vaccinia Ankara (MVA) virus or variant or derivative thereof and mannitol, wherein mannitol is the sole stabilization agent of the composition. The mannitol may provide a stabilizing effect at 0 to +10° C. or in a liquid-frozen composition, for example between ?10° C. and ?30° C. or between ?20° C. and ?23.5° C. The MVA may be used as a vaccine or for use in gene therapy, virotherapy, immunotherapy, or cancer therapy in a mammal, preferably a human.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which encodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Improved vaccines which include a nucleotide sequence that encodes immunomodulating protein operably linked to regulatory elements are disclosed. The improved vaccines include DNA vaccines, recombinant vaccines for delivering foreign antigen and live attenuated vaccines. Methods of immunizing individuals are disclosed. Compositions for and methods of treating individuals with autoimmune diseases are disclosed.

Abstract: Enveloped virus vectors are described which comprise a cellular virus receptor protein and which are capable of fusing with a cell which comprises a viral envelope protein to which the cellular virus receptor protein is cognate. Enveloped virus vectors comprising a plurality of cellular virus receptor proteins are also described. Methods for making the enveloped virus vectors are described, as are methods of using the enveloped virus vectors. The invention further relates to a lipoparticle comprising a membrane spanning protein, and the lipoparticle can be attached to a sensor surface. The invention relates to methods of producing and using the lipoparticle to, inter alia, assess protein binding interactions.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: The present invention encompasses isolated nucleic acids containing transcriptional units which encode a signal sequence of one flavivirus and an immunogenic flavivirus antigen of a second flavivirus. The invention further encompasses a nucleic acid and protein vaccine and the use of the vaccine to immunize a subject against flavivirus infection. The invention also provides antigens encoded by nucleic acids of the invention, antibodies elicited in response to the antigens and use of the antigens and/or antibodies in detecting flavivirus or diagnosing flavivirus infection.

Abstract: The invention relates to Dengue chimeric viruses which are less prone to accumulate point mutations and genetic variations. In these Dengue chimeric viruses, the NS5 gene, which encodes polymerase, has been replaced by the corresponding NS5 sequence of a Yellow Fever virus.

Abstract: The invention concerns the use of a virus for the preparation of a medicament for the vaccination or treatment of a human, wherein the virus is capable of infecting the cells of the human, but not capable of being replicated to infectious progeny virus in the human. The virus is preferably a Modified Vaccinia Virus Ankara.

Abstract: The present invention encompasses isolated nucleic acids containing transcriptional units which encode a signal sequence of one flavivirus and an immunogenic flavivirus antigen of a second flavivirus or of a chimeric immunogenic flavivirus antigen comprising sequence from more than one flavivirus. The invention further encompasses a nucleic acid and protein vaccine and the use of the vaccine to immunize a subject against flavivirus infection. The invention also provides antigens encoded by nucleic acids of the invention, antibodies elicited in response to the antigens and use of the antigens and/or antibodies in detecting flavivirus or diagnosing flavivirus infection.

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: Pharmaceutical compositions including a herpes simplex virus derived composite oncolytic vector are provided for the treatment of solid tumors in an individual. The HSV-derived composite oncolytic vector includes an HSV-derived amplicon defective viral genome carrying at least one toxic foreign gene, and an HSV-derived mutant helper virus vector that has a mutation in the vhs-1 gene. An HSV-derived mutant helper virus vector that has a mutation in the vhs-1 gene is also provided. A method for the treatment of an individual having a solid tumor is provided and includes administering an HSV-derived amplicon defective viral genome including at least one toxic foreign gene, and an HSV-derived mutant helper virus vector including a mutation in the vhs-1 gene.

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.