Crucell Holland B.v.

Introgene B.v.

Galapagos Genomics N.v.

Mucosis B.v.

Het Nederlands Kanker Instituut

Introgene

Govert Johan Schouten

Abraham Bout

Alphonsus G C M UytdeHaag

Ronald Vogels

Domenico Valerio

Maria Grazia Pau

Guus Hateboer

Alphonsus Gerardus Uytdehaag

Karina Cornelia Verhulst

Menzo Jans Emco Havenga

Robert Cornelis Hoeben

Alex Jan Van Der Eb

Frits Jacobus Fallaux

Helmuth Van Es

Jaap Goudsmit

Cornelis Johannes Leenhouts

Markus Peter Einerhand

Ronald H P Brus

Ronald Hans Plasterk

Jan C Vos

Hendricus Gerhard Van Luenen

The invention relates to adjuvanted vaccine formulations, in particular influenza vaccines for intranasal delivery. Provided is an adjuvanted influenza vaccine formulation, comprising (i) peptidoglycan microparticles obtained from a Gram-positive bacterium and (ii) at least one influenza virus antigen or antigenic preparation thereof, which antigen or antigenic preparation is not fused or otherwise covalently attached to a proteinaceous peptidoglycan binding moiety.

Adjuvanted vaccine formulations

Means and methods for producing mammalian viruses, the method comprising infecting a culture of immortalized human cells with a virus, incubating the culture infected with virus to propagate the virus under conditions that permit growth of the virus, and to form a virus-containing medium, and removing the virus-containing medium. The viruses can be harvested and be used for the production of vaccines. Advantages include that human cells of the present invention can be cultured under defined serum-free conditions and the cells show improved capability for propagating virus. Methods are provided for producing, in cultured human cells, influenza virus and vaccines derived thereof. This method eliminates the necessity of using whole chicken embryos for the production of Influenza vaccines. The method also provides for the continuous or batch-wise removal of culture media. As such, the present invention allows the large-scale continuous production of viruses to a high titer.

Production of vaccines

Methods and compositions for the production of recombinant proteins in a eukaryotic cell line are disclosed. The methods and compositions are particularly useful for generating stable expression of recombinant proteins of interest that are modified post-translationally, for example, by glycosylation. Such proteins may have advantageous properties in comparison with their counterparts produced in non-human systems such as Chinese hamster ovary cells.

Recombinant protein production in a human cell

The present invention relates to novel vaccines containing (whole-inactivated) West Nile Viruses and/or West Nile viral proteins derived therefrom, produced on human cells, wherein the human cells comprise a sequence encoding at least one early region-1 (E1) gene product of an adenovirus. The cells are preferably cultured in suspension to very high densities and under serum-free conditions. Herein, it is disclosed that use of such cells results in high titers of West Nile Virus produced.

Vaccines against West Nile Virus

The invention provides a nucleic acid delivery vehicle with or having been provided with at least a tissue tropism for fibroblast-like or macrophage-like cells, preferably synoviocytes. In one aspect, the nucleic acid delivery vehicle is a virus capsid or a functional part, derivative and/or analogue thereof. Preferably, the virus capsid is an adenovirus capsid. Preferably, the adenovirus is a subgroup B adenovirus, such as adenovirus 16. Preferably, the tissue tropism is provided by at least a tissue tropism determining part of an adenovirus fiber protein or a functional derivative and/or analogue thereof. The invention further presents methods for the treatment of diseases, such as joint related diseases.

Means and methods for fibroblast-like or macrophage-like cell transduction

The present invention provides novel methods for determining whether a compound influences a phase in the life cycle of a virus comprising providing a cell with the compound and with at least a fragment of the virus sufficient for performing the phase and determining whether the phase is influenced in the cell, the cell comprising a nucleic acid encoding an adenovirus early protein or a functional part, derivative and/or analogue of the adenovirus early protein. In another aspect, the invention provides the use of a cell, the cell comprising nucleic acid encoding an adenovirus early protein, for screening a library of compounds for the presence of a compound capable of influencing a phase in the life cycle of a virus capable of entering the cell. The invention also provides novel methods for identifying a compound with antiviral activity comprising providing a cell with at least a fragment of a virus, the fragment capable of performing a step in the life cycle of the virus, providing the cell with a compound and determining whether the compound is capable of influencing the step in the life cycle of the virus, wherein the cell comprises a nucleic acid encoding an adenovirus early protein or a functional part, derivative and/or analogue of the adenovirus early protein.

Methods for the identification of antiviral compounds

Methods and compositions for the production of recombinant proteins in a human cell line. The methods and compositions are particularly useful for generating stable expression of human recombinant proteins of interest that are modified post-translationally, for example, by glycosylation. Such proteins may have advantageous properties in comparison with their counterparts produced in non-human systems such as Chinese hamster ovary cells.

Novel means and methods for their use are provided to determine the function of the product(s) of one or more sample nucleic acids. The sample nucleic acids are synthetic oligonucleotides, DNA, or cDNA and encode polypeptides, antisense nucleic acids, or GSEs. The sample nucleic acids are expressed in a host by a vehicle to alter at least one phenotype of the host. The altered phenotype(s) is/are identified as a means to assign a biological function to the product(s) encoded by the sample nucleic acid(s).

High throughput screening of gene function using libraries for functional genomics applications

The invention provides a nucleic acid delivery vehicle with or having been provided with at least a tissue tropism for fibroblast-like or macrophage-like cells, preferably synoviocytes. In one aspect the nucleic acid delivery vehicle is a virus capsid or a functional part, derivative and/or analogue thereof. Preferably, the virus capsid is an adenovirus capsid. Preferably, the adenovirus is a subgroup B adenovirus, preferably adenovirus 16. Preferably, the tissue tropism is provided by at least a tissue tropism determining part of an adenovirus fiber protein or a functional derivative and/or analogue thereof. The invention further presents methods for the treatment of diseases, preferably joint related diseases.

Methods and compositions for the production of recombinant proteins in a human cell line. The methods and positions are particularly useful for generating stable expression of human recombinant proteins of interest that are modified post-translationally, for example, by glycosylation. Such proteins may have advantageous properties in comparison with their counterparts produced in non-human systems such as Chinese Hamster Ovary cells.

The present invention provides chimeric viral vectors which have both the capacity to infect host cells efficiently and the capacity to integrate their genomic material into the host cell's genome. The invention provides a chimeric viral vector which comprises a functional packaging signal derived from a first virus and an integration derived from a second virus. Typically, viruses capable of integrating their material into a host cell genome, having additional genetic material introduced therein by recombinant process, do not have much room for insertion of such additional genetic material or are not very well capable of infecting every wanted host cell. Infecting viruses also lack a high insertion capacity or integration into the host cell's genome. The present invention provides integration of large inserts into a host cell's genome at an efficient infection rate by combining the properties of efficiently infecting viruses with efficiently integrating viruses.

Adeno-associated virus and adenovirus chimeric recombinant viruses useful for the integration of foreign genetic information into the chromosomal DNA of target cells

Cells capable of at least, in part, complementing adenovirus E2A function of an adenovirus defective in E2A function. Such cells include a nucleic acid encoding adenovirus E2A or a functional part, derivative and/or analogue thereof, integrated into the genome of the cell. Preferably, the cell has E2A nucleic acid derived from a temperature sensitive adenovirus such as adenovirus ts125. Methods for producing an adenovirus particle containing an adenovirus vector with a finctional deletion of E2A are also disclosed. Such a method involves providing a cell as previously described with the functionally deleted adenovirus vector, culturing the cell, and harvesting the virus particle. The functional deletion can comprise a deletion of at least part of the nucleic acid encoding E2A. In such a method, the nucleic acid encoding adenovirus E2A in the genome of the cell preferably has no sequence overlap with the vector which leads to replication competent adenovirus and/or to the formation of an adenovirus vector comprising E2A function. In the method, the adenovirus vector preferably further comprises a functional deletion of E1-region encoding nucleic acid. Adenovirus vectors comprising a functional deletion of adenovirus E2A, preferably a deletion of at least part of the nucleic acid encoding E2A are also disclosed. Preparations of adenovirus vector containing adenovirus particles wherein the adenovirus vector comprises a functional deletion of E2A are also disclosed. Such an adenovirus vector preferably further includes a deletion of nucleic acid encoding E1-region proteins, and may be free of adenovirus vectors comprising E2A function. Methods for providing cells of an individual with a nucleic acid of interest, without risk of administering simultaneously a replication competent adenovirus vector, comprising administering the individual one of the previously described preparations are also disclosed.

Growing community of inventors

Leiderdorp, Netherlands

Govert Johan Schouten