Abstract: Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Abstract: The present invention provides recombinant and/or isolated infectious laryngotracheitis virus glycoproteins, including gD, gI, gG and gE.

Abstract: Equine herpesvirus type 1 (EHV-1) causes abortion and respiratory infection in horses. Only certain strains of EHV-1 cause encephalitis. Vaccination of horses with live attenuated or inactivated vaccines against EHV-1 is commonly practiced using commercial vaccine products. None of those vaccines have been tested for protection of horses against neurologic manifestation caused by EHV-1. Clinical evidence indicates that horses vaccinated with the commercial vaccines were protected against the respiratory diseases caused by EHV-1. However, the vaccinated horses were not protected against neurological disease. In this invention, we describe the development of a new inactivated EHV-1 vaccine. The new vaccine will protect vaccinated horses against neurological disease as well as respiratory disease and abortion caused by EHV-1. The vaccine will use a newly isolated Findlay strain of EHV-1 as the master seed virus.

Abstract: Superior molecular vaccines comprise nucleic acids, including naked DNA and replicon RNA, that encode a fusion polypeptide that includes an antigenic peptide or polypeptide against which an immune response is desired. Fused to the antigenic peptide is an intercellular spreading protein, in particular a herpes virus protein VP22 or a homologue or functional derivative thereof. Preferred spreading proteins are VP22 from HSV-1 and Marek's disease virus. The nucleic acid can encode any antigenic epitope of interest, preferably an epitope that is processed and presented by MHC class I proteins. Antigens of pathogenic organisms and cells such as tumor cells are preferred. Vaccines comprising HPV-16 E7 oncoprotein are exemplified. Also disclosed are methods of using the vaccines to induce heightened T cell mediated immunity, in particular by cytotoxic T lymphocytes, leading to protection from or treatment of a tumor.

Abstract: This invention relates to Equine Herpes Viruses (EHV) wherein the protein gM is essentially absent or modified and non-functional with respect to its immunomodulatory capacity. Further aspects of the invention relate to nucleic acids coding said viruses, pharmaceutical compositions comprising these viruses or nucleic acids and uses thereof. The invention also relates to methods for improving the immune response induced by an EHV vaccine against wild type EHV infections, methods for the prophylaxis and treatment of EHV infections and methods for distinguishing wild type EHV infected animals from animals treated with EHV's according to the invention.

Abstract: An attenuated feline recombinant herpesvirus 1 (FHV-1), which is prepared by identifying gene regions in the genome wherein inserted foreign genes can be expressed without affecting the replication of FHV-1 and has least two types of foreign nucleic acid sequences inserted thereinto, usable as a vector virus or a vaccine. In this attenuated recombinant FHV-1, at least two types of foreign genes are inserted in such a manner as allowing the expression into two different gene regions exerting no lethal effect on the proliferation of the virus in the feline herpesvirus 1 genome.

Abstract: The present invention relates to nanoparticle vaccines comprised of a carrier, particularly polymerized lipids, having multiple copies of an antigen or combinations of different antigens displayed on the carrier. Such antigen-displaying nanoparticles may also display a targeting molecule on its surface in order to direct it to a specific site or cell type to optimize a desired immune response. The present invention also relates to encapsulating an antigen or combinations of different antigens within such nanoparticles, with or without a targeting molecule displayed on its surface. The antigens used in this invention are effective to produce an immune response against a variety of pathological conditions.

Abstract: The present invention involves a recombinant virus which comprises at least one foreign nucleic acid inserted within a non-essential region of the viral genome of a virus, wherein each such foreign nucleic acid encodes a protein. The protein which is encoded is selected from the groups consisting of a feline CD28 protein or an immunogenic portion thereof, a feline cD80 protein or an immunogenic portion thereof, a feline CD86 protein or an immunogenic portion thereof, or a feline CTLA-4 protein or an immunogenic portion thereof. The protein is capable of being expressed when the recombinant virus is introduced into an appropiate host. The present invention also involves a recombinant virus further comprising a foreign nucleic acid encoding an immunogen derived from a pathogen. The present invention also comprises recombinant viruses which are capable of enhancing an immune response in a feline.

Abstract: The present invention provides a herpes virus in which a non-essential gene for replication is inactivated More particularly, the present invention provides a herpes virus in which a non-essential gene for replication present in a UL or US region is inactivated. More preferably, the non-essential gene for replication contains US3 or UL56. The herpes virus may be preferably a herpes simplex virus, and more preferably herpes simplex virus 1 or herpes simplex virus 2. The present invention provides a method, composition and use for treating various diseases or disorders including tumor and infectious diseases. The present invention also provides a method, composition and use for activating a prodrug.

Abstract: Disclosed is an invention related to the preparation and use of vaccines against pathogenic organisms, such as herpes virus. The vaccines hereof are based upon the use of truncated, membrane-free derivatives of a membrane-bound polypeptide from the pathogen. These polypeptides when incorporated into a vaccine composition afford protection against pathogenic challenge after administration.

Abstract: A vaccine for protecting a horse against diseases associated with EHV-1 and/or EHV-4 is provided. The vaccine commonly includes inactivated EHV-1 (e.g., chemically inactivated EHV-1 KyA virus) and an adjuvant. The adjuvant can include a cross-linked olefinically unsaturated carboxylic acid polymer which may have bioadhesive properties. The vaccine may also include antigens against other equine pathogens such as inactivated EHV-4 and inactivated A1 and/or A2 strains of equine influenza virus. Methods for protecting horses against diseases associated with EHV-1 and/or EHV-4 and methods of producing the equine herpesvirus vaccine are also provided.

Abstract: A herpesvirus vaccine comprising a mutated herpesvirus suspended in a pharmaceutically acceptable carrier. The mutated herpesvirus is capable of infecting cells of the mammal to be vaccinated, but incapable of completing a replicative cycle, and it is capable of eliciting a protective immune response in that mammal. The mutated herpesvirus is also capable of treating immunomodulatory or immunoregulatory diseases. The mutation occurs in at least one gene encoding a protein essential for replication of the virus, so that the mutation renders the virus replication defective.

Abstract: An effective vaccine for Marek's disease may be prepared using a viral agent which is a Marek's disease virus unable to express a functional meq protein. This viral agent is effective to elicit an immune response in a chicken to very virulent strains of Marek's disease virus without causing a significant degree of pathogenicity in the inoculated bird. Suitable formulations of the vaccine for use in chickens include an effective immunization dosage of this novel viral agent with a pharmaceutically acceptable carrier or diluent.

Abstract: DNA and protein constructs useful in producing vaccines against human cytomegalovirus contain optionally N-end modified and N-terminal ubiquitinated human cytomegalovirus antigenic proteins, including pp65, pp150, IE1, gB and antigenic fragments thereof. Vaccine viruses, in particular poxviruses such as vaccinia and Modified Vaccinia Ankara, that express the constructs may be used as vaccines to augment the immune response to human cytomegalovirus, both prophylatically and in patients already carrying human cytomegalovirus, as well as to create and expand cytomegalovirus-reactive T cells for transfer of adoptive immunity.

Abstract: The present invention relates to the field of animal health and in particular of Equine Herpes Viruses (EHV) wherein the gene encoding the protein gM is absent, and which is free of heterologous elements. Further aspects of the invention relate to pharmaceutical compositions comprising said viruses, uses thereof, and methods for the prophylaxis and treatment of EHV infections. The invention also relates to pharmaceutical compositions comprising the combination of EHV-1 and EHV-4 viruses wherein the gene encoding the protein gM is absent and which is free of heterologous elements.

Abstract: An attenuated herpes virus which lacks a functional vhs gene or a functional equivalent thereof, but which has a functional UL43 gene or functional equivalent thereof, stimulates an immune response when dendritic cells are infected with the virus.

Abstract: Described is a method of identifying an immunologically active antigen of a virus that attacks skin, as well as a method of enriching a population of lymphocytes for T lymphocytes that are specific to a virus that attacks skin. Also provided are HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection that have been identified via the methods of the invention. 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: A method of stimulating an immune response in a human or animal subject, which method comprises administering to a subject in need thereof an effective amount of an attenuated herpes virus which: (i) lacks a functional vhs gene, or a functional equivalent thereof; (ii) lacks a functional ICP47 gene, or a functional equivalent thereof; and (iii) is incapable of expressing a substantial amount of functional ICP22, or a functional equivalent thereof, in mammalian dendritic cells.

Abstract: The present invention relates to novel Equine herpesvirus (EHV) mutants comprising one or more deletions, substitutions, or insertions in the endogenous promoter region of an essential viral gene, preferably the immediate early gene of EHV. The EHV mutants are stable and have reduced virulence, which makes them very suitable for use in a live vaccine. The invention furthermore relates to live vaccines comprising said EHV mutants, to DNA sequences and vectors harbouring a mutated EHV sequence, to host cells transfected with said DNA or vectors. The invention also relates to a method of attenuating EHV in general, and EHV-1 in particular.

Abstract: The present invention provides recombinant and/or isolated infectious laryngotracheitis virus glycoproteins, including gD, gl, gG and gE.

Abstract: The present invention includes novel recombinant canine herpes virus (CHV) and novel recombinant CHV genomes, and particularly to those CHV and CHV genomes that contain heterologous nucleic acid molecules. The present invention also relates to the use of such genomes and viruses in a variety of applications, including as therapeutic compositions to protect animals from disease. The present invention also relates to novel isolated CHV nucleic acid molecules, to CHV proteins encoded by such nucleic acid molecules, and to antibodies raised against such CHV proteins as well as to the use of such CHV nucleic acid molecules, proteins and antibodies as therapeutic compositions to protect an animal from CHV. The present invention also includes constructs comprising CHV nucleic acid molecules that include heterologous nucleic acid molecules, to recombinant vectors including such constructs, and to the use of such constructs and vectors in the production of recombinant CHV and recombinant CHV genomes.

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

Abstract: The present invention provides a vaccine accelerator factor (VAF) which is an in ovo nucleotide immuno-stimulant. The VAF contains one or more DNA constructs, each having a DNA molecule and a vector. Each of the DNA molecule contains one or more genes or gene fragments, each encoding an antigenic peptide of an avian virus. The VAF is preferably administered to the amniotic fluid of an egg after being fertilized for about 17–19 days. The VAF can be co-administered with a viral vaccine containing one or more attenuated or inactive avian viruses. Alternatively, the VAF can be administered prior to the administration of the viral vaccine, which is administered at hatch or post-hatch. The VAF stimulates and accelerate a protective immune response of a viral vaccine.

Abstract: The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent induces of a range of immune responses.

Abstract: The present invention relates to the identification of a subunit vaccine to prevent or treat infection of Epstein Barr Virus. In particular, EBNA-1 was identified as a vaccine antigen. In a specific embodiment, a purified protein corresponding to EBNA-1 elicited a strong CD4+ T cell response. The responsive CD4+ T cell are primarily TH1 in function. EBNA-1 is an attractive candidate for a protective vaccine against EBV, and for immunotherapy of EBV infection and neoplasms, particularly with dendritic cells charged with EBNA-1.

Abstract: Methods of nucleic acid immunization comprising the in utero delivery of nucleic acid molecules that encode one or more selected antigens to a vertebrate fetus are disclosed.

Abstract: Isolated polynucleotides and polypeptides derived from the genome of swine gamma-herpesviruses are disclosed, including recombinant cells and vectors encoding such polypeptides and expressing such polynucleotides. Use of the novel polynucleotides as probes of the swine genome is also described. Assay methods employing antibodies against the isolated polypeptides are also disclosed.

Abstract: A specific binding agent is provided, wherein the specific binding agent specifically binds Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), and the specific binding agent neutralizes an activity of vIL-6. In one embodiment, the specific binding agent is an antibody. Methods are provided for using a specific binding agent that binds vIL-6, and neutralizes a biological activity of vIL-6. Methods of treatment for a KSHV-associated disorder are also provided. Methods for diagnosing a KSHV-associated disorder are provided, as are kits that include a specific binding agent of the invention. A method is also provided for testing an agent for effectiveness in treating a KSHV-associated disorder. The method includes incubating the agent with a cell free system comprising a vIL-6 receptor component and vIL-6, and comparing the binding of vIL-6 and the receptor component in the presence of the agent to binding of vIL-6 to the receptor component in the absence of the agent.

Abstract: Novel combined vaccine composition preferentially for administration to adolescents are provided, comprising a hepatitis B viral antigen and a herpes simplex viral antigen and optionally in addition one or more of the following: an EBV antigen, a hepatitis A antigen or inactivated attenuated virus, an HPV antigen, a V2V antigen, a HCMV antigen, a Toxoplasma gondii antigen. The vaccine compositions are formulated with an adjuvant which is a preferential stimulator of TH1 cell response such as 3D-MPL and QS21.

Abstract: The invention concerns an immunogenic peptide comprising at least six consecutive amino acids of a hydrophilic region of the glycoprotein B (gB) of the human herpesvirus-7 (HIV-7), and reacting specifically with antibodies directed against HHV-7, and diagnosis kit containing it.

Abstract: The present invention provides a novel avian herpesvirus (NAHV) vector and recombinant vaccines made therefrom that are useful to immunize avian species against Marek's disease, infectious laryngotracheitis and Newcastle disease. Methods of immunizing an avian species against Marek's disease, infectious laryngotracheitis and Newcastle disease are also provided.

Abstract: The subject invention provides a fusion protein for producing a dual immune response in a vertebrate, which fusion protein comprises: (a) a first proteinaceous portion analogous to all or part of a peptide endogenously synthesized within the vertebrate, the activity of which peptide is to be inhibited within the vertebrate, and which proteinaceous portion by itself is incapable of eliciting an effective immunoinhibitory response in said vertebrate; connected to (b) a second proteinaceous portion analogous to all or part of an immunogen from a pathogen, which pathogen is capable of pathogenically infecting the vertebrate; the portion (b) causing the vertebrate's immune system to recognize the portion (a) and produce a response that: (i) inhibits the activity of the peptide endogenously synthesized within the vertebrate; and (ii) protects the vertebrate from infection by the pathogen, when the vertebrate is vaccinated with an effective amount of the fusion protein.

Abstract: The invention relates to a vaccine against herpes simplex virus (HSV) comprising an invasive but attenuated or non-pathogenic bacterium, which bacterium comprises a coding sequence encoding a HSV antigen in a form that enables said coding sequence to be transferred to a host cell of a human or animal host which the bacterium is capable of invading and to be expressed in said cell to form said antigen without the introduction of an antimicrobial agent to lyse the bacterium. The invention also provides similar vaccines against other viruses.

Abstract: A vaccine having a good vaccination effect, which comprises an antigen; a peptide selected from the group consisting of a peptide having the amino acid sequence of SEQ ID NO: 1, a peptide having the amino acid sequence of SEQ ID NO: 2, and a peptide derived from a peptide having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2; and an immune activator.

Abstract: Recombinant, attenuated infectious laryngotracheitis viruses containing a deletion or deletions in a glycoprotein gene are provided. Also provided are glycoprotein genes, gD, gI, gG and gE as well as other viral genes.

Abstract: The present invention provides a recombinant herpesvirus of turkeys modified by the presence of cDNA encoding the F protein of Newcastle disease virus under the control of a promoter. The poultry vaccine consisting of the recombinant herpesvirus of turkeys of the present invention can induce in chickens protective immunity against Newcastle disease virus.

Abstract: A method for inducing and enhancing protective and/or therapeutic immunity in a mammal to HSV includes the steps of at least one immunization with an effective amount of a DNA vaccine composition which comprises a first nucleic acid molecule comprising a DNA sequence encoding the HSV type 1 or type 2 gD protein, and a second nucleic acid molecule comprising a DNA sequence encoding each Interleukin-12 heterodimer subunit. The method also comprises at least one subsequent immunization with an effective amount of a protein vaccine composition which comprises the HSV type 1 or type 2 gD protein; and the IL-12 heterodimer. A local anesthetic may be included in the DNA vaccine composition in an amount that forms one or more complexes with the nucleic acid molecules. When provided to the mammal in suitable effective dosages according to this protocol, the vaccine compositions used in this method produce an unexpectedly good protective and/or therapeutic immune response against HSV in an immunized mammal.

Abstract: This invention provides an isolated nucleic acid which encodes a Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 2 polypeptide (LANA2) or a fragment thereof and also provides the LANA2 polypeptide. This invention provides an isolated nucleic acid comprising consecutive nucleotides having the sequence of a promoter of Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 2 transcription. This invention also provides a method of inhibiting p53 mediated apoptosis of a cell and a method of producing an antibody which comprises introducing into a cell a replicable vector of the subject invention.

Abstract: The present invention provides methods of expressing a nucleic acid or producing a proteinaceous composition encoded by a nucleic acid in vascular and cardiovascular cells by administration of a herpesvirus vector. The present invention provides methods of producing a therapeutic benefit in vascular and cardiovascular tissue by administration of a herpesvirus vector. In additional aspects, the invention concerns combination therapies for vascular and cardiovascular diseases comprising administration of a herpesvirus vector and treatment with at least one addition pharmacological agent or surgical procedure.

Abstract: A pharmaceutical composition comprises M3 protein as encoded by virus MHV 68, or a homologue of said M3 protein, for use in binding to a chemokine or a chemokine analogue in vivo, or to block binding of chemokines to corresponding cell surface receptors in vivo, to produce an immunomodulatory effect, or to bind to a chemokine analogue present in a virus or parasite to block its entry into cells.

Abstract: The present invention provides a herpes virus in which a non-essential gene for replication is inactivated. More particularly, the present invention provides a herpes virus in which a non-essential gene for replication present in a UL or US region is inactivated. More preferably, the non-essential gene for replication contains US3 or UL56. The herpes virus may be preferably a herpes simplex virus, and more preferably herpes simplex virus 1 or herpes simplex virus 2. The present invention provides a method, composition and use for treating various diseases or disorders including tumor and infectious diseases. The present invention also provides a method, composition and use for activating a prodrug.

Abstract: The present invention provides recombinant and/or isolated infectious laryngotracheitis virus glycoproteins, including gD, gl, gG and gE.

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

Abstract: The present invention relates to methods for treating or preventing diseases or disorders in a pregnant cow and calf nursing a pregnant cow caused by infection by Bovine Viral Diarrhea Virus (BVDV) Types 1 and 2, Bovine Herpes Virus Type-1 (BHV-1), Bovine Respiratory Syncytial Virus (BRSV), Parainfluenza Virus (PIV3), Campylobacter fetus, Leptospira canicola, Leptospira grippotyphosa, Leptospira hardj-prajitno, Leptospira icterohaemmorrhagiae, Leptospira hardjo-bovis and Leptospira pomona by administering to the animal an effective amount of a safe modified live viral combination vaccine further combined with a multivalent bacterin vaccine.

Abstract: A vaccine for protecting a horse against diseases associated with EHV-1 and/or EHV-4 is provided. The vaccine commonly includes inactivated EHV-1 (e.g., chemically inactivated EHV-1 KyA virus) and an adjuvant. The adjuvant can include a cross-linked olefinically unsaturated carboxylic acid polymer which may have bioadhesive properties. The vaccine may also include antigens against other equine pathogens such as inactivated EHV-4 and inactivated A1 and/or A2 strains of equine influenza virus. Methods for protecting horses against diseases associated with EHV-1 and/or EHV-4 and methods of producing the equine herpesvirus vaccine are also provided.

Abstract: The cloning of a novel PCVII viral genome is described as is expression of proteins derived from the PCVII genome. These proteins can be used in vaccine compositions for the prevention and treatment of PCVII infections, as well as in diagnostic methods for determining the presence of PCVII infections in a vertebrate subject. Polynucleotides derived from the viral genome can be used as diagnostic primers and probes.

Abstract: This invention relates to Equine Herpes Viruses (EHV) wherein the protein gM is essentially absent or modified and non-functional with respect to its immunomodulatory capacity. Further aspects of the invention relate to nucleic acids coding said viruses, pharmaceutical compositions comprising these viruses or nucleic acids and uses thereof. The invention also relates to methods for improving the immune response induced by an EHV vaccine against wild type EHV infections, methods for the prophylaxis and treatment of EHV infections and methods for distinguishing wild type EHV infected animals from animals treated with EHV's according to the invention.

Abstract: An attenuated herpes virus which lacks a functional vhs gene or a functional equivalent thereof, but which has a functional UL43 gene or functional equivalent thereof, stimulates an immune response when dendritic cells are infected with the virus.

Abstract: This invention relates to Equine Herpes Viruses (EHV) wherein the protein gM is essentially absent or modified and non-functional with respect to its immunomodulatory capacity. Further aspects of the invention relate to nucleic acids coding said viruses, pharmaceutical compositions comprising these viruses or nucleic acids and uses thereof. The invention also relates to methods for improving the immune response induced by an EHV vaccine against wild type EHV infections, methods for the prophylaxis and treatment of EHV infections and methods for distinguishing wild type EHV infected animals from animals treated with EHV's according to the invention.

Abstract: Primary effusion lymphoma (PEL) cells harbor Kaposi's sarcoma-associated herpesvirus (KSHV) episomes and express a KSHV encoded latency-associated nuclear antigen (LANA). In PEL cells, LANA and KSHV DNA co-localized in dots in interphase nuclei and along mitotic chromosomes. In the absence of KSHV DNA, LANA was diffusely distributed in the nucleus or on mitotic chromosomes. In lymphoblasts, LANA was necessary and sufficient for the persistence of episomes containing a specific KSHV DNA fragment. Furthermore, LANA co-localized with the artificial KSHV DNA episomes in nuclei and along mitotic chromosomes. The KSHV DNA segment that provides for efficient persistence in LANA positive cells has been identified as the rhodino virus cis-acting element (RVCAE). These results support a model in which LANA tethers episomes containing the KSHV RVCAE DNA to chromosomes during mitosis to enable efficient segregation to progeny cells.