Abstract: A platform enabling the manufacture of thermostable vaccines by incorporating recombinantly expressed, viral envelope proteins in their native conformation into ether glycerophospholipid nanodisc structures that simulate the natural environment of the envelope proteins. The ether glycerophospholipids include ether-linked hydrophobic side chains, and are derived from or modeled after those found in thermophile bacteria, which increase thermostability, thereby significantly enhancing the vaccine's potency, enabling the production of highly multivalent vaccines incorporating multiple variants of the viral antigen, and improving stability and shelf-life.

Abstract: A platform enabling the manufacture of thermostable vaccines by incorporating recombinantly expressed, viral envelope proteins in their native conformation into ether glycerophospholipid nanodisc structures that simulate the natural environment of the envelope proteins. The ether glycerophospholipids include ether-linked hydrophobic side chains, and are derived from or modeled after those found in thermophile bacteria, which increase thermostability, thereby significantly enhancing the vaccine's potency, enabling the production of highly multivalent vaccines incorporating multiple variants of the viral antigen, and improving stability and shelf-life.

Abstract: A packaging cell line that complements recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line may be derived from primary, diploid human cells that are transformed by adenovirus E1 sequences either operatively linked on one DNA molecule or located on two separate DNA molecules, the sequences being operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also disclosed is a cell line derived from PER.C6® that expresses functional Ad35 E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter or a heterologous promoter and terminated by a heterologous poly-adenylation signal. The cell lines are useful for producing recombinant adenoviruses designed for gene therapy and vaccination, and can also be used for producing human recombinant therapeutic proteins such as human growth factors and human antibodies.

Abstract: A packaging cell line that complements recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line may be derived from primary, diploid human cells that are transformed by adenovirus E1 sequences either operatively linked on one DNA molecule or located on two separate DNA molecules, the sequences being operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also disclosed is a cell line derived from PER.C6® that expresses functional Ad35 E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter or a heterologous promoter and terminated by a heterologous poly-adenylation signal. The cell lines are useful for producing recombinant adenoviruses designed for gene therapy and vaccination, and can also be used for producing human recombinant therapeutic proteins such as human growth factors and human antibodies.

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. Also described is 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. Further described is 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.

Abstract: A packaging cell line that complements recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line is preferably derived from primary, diploid human cells that are transformed by adenovirus E1 sequences either operatively linked on one DNA molecule or located on two separate DNA molecules, the sequences being operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also disclosed is a cell line derived from PER.C6 that expresses functional Ad35 E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter or a heterologous promoter and terminated by a heterologous poly-adenylation signal. The cell lines are useful for producing recombinant adenoviruses designed for gene therapy and vaccination. The cell lines can also be used for producing human recombinant therapeutic proteins such as human growth factors and human antibodies.

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: Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.

Abstract: Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is 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. Also described is 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.

Abstract: In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. Provided are means and methods for reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.

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

Abstract: Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is 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. Also described is 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.

Abstract: Provided are methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B-55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.

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. Also described is 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. Further described is 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.

Abstract: In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. Provided are means and methods for reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.

Abstract: In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. The invention provides means and methods reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.

Abstract: The present invention relates to recombinant adenoviral vectors based on adenoviruses that encounter pre-existing immunity in a minority of the human population and which harbor a chimeric capsid. The chimeric capsid comprises fiber proteins that have at least the knob domain of a human adenovirus that binds to the Coxsackievirus and Adenovirus Receptor (CAR) and a hexon protein from an adenovirus serotype that encounters pre-existing immunity in a low percentage of the human population.

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

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.