Abstract: The invention provides methods for propagating a monkey adenovirus in a cell including a human cell, comprising one or more gene products isolated from a human adenovirus. Also provided are methods for propagating wherein the monkey adenovirus comprises a nucleic acid sequence encoding a human adenovirus gene product. The invention further provides a monkey adenovirus. including a replication-deficient monkey adenovirus, obtained by such propagation methods.

Abstract: The invention provides a method for treating cancer in a human comprising administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding TNF-? operably linked to a promoter, wherein the dose comprises about 1×107 to about 4×1012 particle units (pu) of replication-deficient adenoviral vector, at least once in a therapeutic period comprising up to 10 weeks, whereby the cancer in human is treated. The invention further provides a method of treating a human for multiple tumors, wherein the method comprises contacting a first tumor with a dose of the pharmaceutical composition at least once in a therapeutic period comprising up to about 10 weeks, whereby the human is treated for the first tumor and one or more additional tumors.

Abstract: The invention provides a method for treating locally advanced resectable esophageal cancer in a human comprising (a) administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding a human TNF-? and operably linked to a promoter, wherein the dose comprises about 4×107 to about 4×1012 particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, (b) administering a dose of ionizing radiation to the human over the duration of the therapeutic period, and (c) administering a dose of one or more chemotherapeutics to the human over the duration of the therapeutic period, whereby the locally advanced resectable esophageal cancer in the human is treated.

Abstract: In one embodiment, the invention provides a multiclade HIV plasmid DNA or viral vector vaccine including components from different clades of Env (optionally Env chimeras) and Gag-Pol-(optionally)Nef from a singlr clade. The vaccine of the invention may further include V1, V2, V3, or V4 deletions or combinations thereof. In another embodiment, the invention provides multiclade HIV envelope immunogens.

Abstract: The present disclosure provides compositions for eliciting an immune response, including a prophylactic immune response, against human immunodeficiency virus. The composition includes nucleic acid constructs encoding HIV antigenic polypeptides of multiple clades or strains. Methods for eliciting an immune response by administering the composition to a subject are also provided.

Abstract: The invention is directed to a live attenuated serotype 14 adenovirus, and a method of inducing an immune response against a serotype 14 adenovirus in a mammal using the live attenuated serotype 14 adenovirus.

Abstract: The invention provides a method for treating cancer in a human comprising (a) administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding a human TNF-? and operably linked to a promoter, wherein the dose comprises about 4×107 to about 4×1012 particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, (b) administering a dose of ionizing radiation to the human over the duration of the therapeutic period, and (c) administering a dose of one or more chemotherapeutics to the human over the duration of the therapeutic period, whereby the cancer in the human is treated.

Abstract: The invention provides a method for treating cancer in a human comprising administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding TNF-? operably linked to a promoter, wherein the dose comprises about 1×107 to about 4×1012 particle units (pu) of replication-deficient adenoviral vector, at least once in a therapeutic period comprising up to 10 weeks, whereby the cancer in human is treated. The invention further provides a method of treating a human for multiple tumors, wherein the method comprises contacting a first tumor with a dose of the pharmaceutical composition at least once in a therapeutic period comprising up to about 10 weeks, whereby the human is treated for the first tumor and one or more additional tumors.

Abstract: The invention provides a method of inducing an immune response against a human immunodeficiency virus (HIV) in a mammal. The method comprises administering to the mammal an adenoviral vector composition comprising one or more adenoviral vectors encoding two or more different HIV antigens, the production of which induces an immune response against HIV in the mammal. The invention also provides an adenoviral vector composition comprising four adenoviral vectors encoding an HIV clade A Env protein, an HIV clade B Env protein, an V clade C Env protein, and a fusion protein comprising an HIV clade B Gag protein and Pol protein, respectively.

Abstract: The invention is directed to an adenoviral vector comprising at least one nucleic acid sequence encoding an aphthovirus antigen and/or a cytokine operably linked to a promoter. The adenoviral vector is replication-deficient and requires at most complementation of both the E1 region and the E4 region of the adenoviral genome for propagation. The invention also is directed to a method of inducing an immune response in a mammal comprising administering to the mammal a composition comprising the aforementioned adenoviral vector.

Abstract: The invention provides methods of inhibiting angiogenesis within a tissue, promoting neuron protection within a tissue, and treating a disease in a mammal, wherein (a) a gene transfer vector encoding a protein of a serpin superfamily or a therapeutic fragment or variant thereof or (b) a protein of a serpin superfamily or a therapeutic fragment or variant thereof is administered with an inhibitor of matrix metalloprotease (MMP). Alternatively, the method comprises administration of (a) a protein of a serpin superfamily or therapeutic fragment or variant thereof or (b) a gene transfer vector encoding a protein of a serpin superfamily or a therapeutic fragment or variant thereof, wherein the protein or nucleic acid encoding the protein comprises at least one mutation which renders the protein of the serpin superfamily resistant to cleavage by an MMP.

Abstract: The invention provides adenoviral vectors comprising an adenoviral genome comprising heterologous antigen-encoding nucleic acid sequences, such as Plasmodium nucleic acid sequences, operably linked to promoters. The invention further provides a method of inducing an immune response against malaria in a mammal comprising administering the adenoviral vectors to the mammal.

Abstract: The invention is directed to a method of delivering a gene product to an animal. The method comprises administering an expression vector comprising a nucleic acid sequence operably linked to a promoter and encoding a gene product, and upregulating transcription of the nucleic acid sequence in the ocular cell. The expression vector can be an adenoviral vector. The invention further provides a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a neurotrophic agent. In one aspect, the method further comprises upregulating transcription of the nucleic acid sequence. Preferably, if 2×108 adenoviral particles of the inventive method are administered to a mouse, the level of expression of the nucleic acid sequence is not diminished more than ten-fold at 28 days post-administration.

Abstract: The present invention is directed to a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder, e.g., ocular neovascularization or age-related macular degeneration. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and the same or different nucleic acid sequence encoding a neurotrophic agent. The method also can comprise contacting an ocular cell with different expression vectors, each comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a nucleic acid sequence encoding a neurotrophic agent. In addition, the present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof.

Abstract: The invention provides a method of inducing an immune response against malaria in a mammal. The method comprises intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of (a) a first adenoviral vector comprising a nucleic acid sequence encoding a P. falciparum circumsporozoite protein (CSP) operably linked to a human CMV promoter, and/or (b) a second adenoviral vector comprising a nucleic acid sequence encoding a P. falciparum apical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter.

Abstract: The invention provides a method of propagating an adenoviral vector. The method comprises (a) providing a cell comprising a cellular genome comprising a nucleic acid sequence encoding a tetracycline operon repressor protein (tetR), and (b) contacting the cell with an adenoviral vector comprising a heterologous nucleic acid sequence encoding a toxic protein. The heterologous nucleic acid sequence is operably linked to a promoter and one or more tetracycline operon operator sequences (tetO), and expression of the heterologous nucleic acid sequence is inhibited in the presence of tetR, such that the adenoviral vector is propagated. The invention also provides a system comprising the aforementioned cell and adenoviral vector.

Abstract: The invention provides a method of inducing an immune response in a mammal. The method comprises administering to the mammal an adenoviral vector comprising (a) a subgroup C fiber protein wherein a native coxsackievirus and adenovirus receptor (CAR)-binding site is disrupted, (b) a subgroup C penton base protein wherein a native integrin-binding site is disrupted, and (c) a nucleic acid sequence encoding at least one antigen derived from an infectious agent other than an adenovirus which is expressed in the mammal to induce an immune response.

Abstract: The invention provides a gene transfer vector and a conjugate comprising at least three contiguous amino acids of a shaft region of a subgroup C adenovirus fiber protein. The invention also provides methods of using the gene transfer vector and the conjugate to induce an immune response in a mammal, and to deliver a protein or a non-proteinaceous molecule to a specific cell type.

Abstract: The invention provides methods of inhibiting angiogenesis within a tissue, promoting neuron protection within a tissue, and treating a disease in a mammal, wherein (a) a gene transfer vector encoding a protein of a serpin superfamily or a therapeutic fragment or variant thereof or (b) a protein of a serpin superfamily or a therapeutic fragment or variant thereof is administered with an inhibitor of matrix metalloprotease (MMP). Alternatively, the method comprises administration of (a) a protein of a serpin superfamily or therapeutic fragment or variant thereof or (b) a gene transfer vector encoding a protein of a serpin superfamily or a therapeutic fragment or variant thereof, wherein the protein or nucleic acid encoding the protein comprises at least one mutation which renders the protein of the serpin superfamily resistant to cleavage by an MMP.

Abstract: The invention provides a method of inducing an immune response against a human immunodeficiency virus (HIV) in a mammal. The method comprises administering to the mammal an adenoviral vector composition comprising one or more adenoviral vectors encoding two or more different HIV antigens, the production of which induces an immune response against HIV in the mammal. The invention also provides an adenoviral vector composition comprising four adenoviral vectors encoding an HIV clade A Env protein, an HIV clade B Env protein, an HIV clade C Env protein, and a fusion protein comprising an HIV clade B Gag protein and Pol protein, respectively.