Genvec, Inc.

USA As Represented by Secretary of the Navy

Other

Cornell Research Foundation Inc.

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

Joseph T Bruder

Imre Kovesdi

Douglas E Brough

Duncan L McVey

Thomas J Wickham

C Richter King

Petrus W Roelvink

Alena Lizonova

Denise Louise Doolan

Ping Chen

Keith Limbach

Daniel John Carucci

Erik S Falck-Pedersen

Jason Gall

Martha Sedegah

Joao Carlos Aguair

Walter R Weiss

Marvin J Grubman

Damodar R Ettyreddy

John Neilan

Thomas L Richie

Duncan Mcvey

The invention is directed to a composition comprising one or more polypeptides or one or more nucleic acid sequences that can induce a protective immune response againstspecies that infect humans. The invention also is directed to a method of using such compositions to induce a protective immune response against aparasite in a mammal.

Malaria antigens and methods of use

The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.

Malaria antigen screening method

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 acircumsporozoite protein (CSP) operably linked to a human CMV promoter, and/or (b) a second adenoviral vector comprising a nucleic acid sequence encoding aapical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter.

Adenoviral vector-based malaria vaccines

The invention relates to a replication-deficient adenoviral vector comprising two or more nucleic acid sequences encoding Dengue virus antigens and a chimeric hexon protein. The chimeric hexon protein comprises a first portion and a second portion. The first portion comprises at least 10 contiguous amino acid residues from a first adenovirus serotype (e.g., serotype 5 adenovirus hexon protein), optionally with one amino acid substitution. The second portion comprises (a) at least one hypervariable region (HVR) of a hexon protein of an adenovirus of a second adenovirus serotype, or (b) at least one synthetic hypervariable region (HVR) that is not present in the hexon protein of the wild-type adenovirus of the first adenovirus serotype.

Adenoviral vector-based dengue fever vaccine

The invention provides adenoviral vectors comprising an adenoviral genome comprising heterologous antigen-encoding nucleic acid sequences, such asnucleic 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.

The invention is directed to an adenoviral vector comprising at least one nucleic acid sequence encoding anantigen 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.

Adenoviral vector-based foot-and-mouth disease vaccine

The present invention provides multiply deficient adenoviral vectors and complementing cell lines. Also provided are recombinants of the multiply deficient adenoviral vectors and a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such recombinants.

Complementary adenoviral vector systems and cell lines

The present invention provides a library of viral vectors, wherein each member comprises a first heterologous DNA encoding a first gene product and a second heterologous DNA encoding a second gene product. The first heterologous DNA is common to each member of the library, while the second heterologous DNA varies between members of the library. The present invention additionally provides a method of constructing a library of viral vectors. The method comprises carrying out homologous recombination between a first DNA molecule and a second DNA molecule to form a pool of intermediate viral vector genomes. One or more linear third DNA molecules are ligated into the pool of intermediate viral genomes to produce a library of viral vector genomes. Alternatively, homologous recombination between linear DNA molecules and recipient DNA molecules produces a library of viral vector genomes. The library of viral vector genomes is converted into a library of viral vectors.

Methods of preparing and using a viral vector library

The present invention provides a complex that includes a virion having a ligand that recognizes an epitope present on an immune effector cell surface and at least a first nucleic acid encoding a first non-native antigen. The invention also provides a library including a plurality of such complexes, in which antigens of at least two of the plurality are different. Using such reagents, the invention provides a method of precipitating an immune response within an immune effector cell, wherein such a complex is delivered to the cell under conditions sufficient for the cell to mount an immune response to the antigen. When applied in vivo, the method can serve to immunize an animal from the pathogen. Moreover, using a library including a plurality of complexes, which contains at least one test antigen, the invention provides a method of assessing the antigenicity of the test antigen.

Antigenic complexes and methods

The present invention provides methods for administering an adenoviral gene transfer vector comprising an exogenous gene to an animal. One method involves utilizing systemic neutralizing antibodies to neutralize the adenoviral gene transfer vector outside a targeted muscle. Another method involves the repeat administration of an adenoviral gene transfer vector to a skeletal muscle.

Methods of administering adenoviral vectors

The invention provides a chimeric adenovirus fiber protein including a nonnative amino acid sequence, and a chimeric adenovirus fiber protein lacking a native amino acid receptor-binding sequence. The chimeric protein trimerizes when produced in a mammalian cell.

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Ijamsville, MD, United States of America

Joseph T Bruder