Crucell Holland B.v.

Lennart Holterman

Maria Grazia Pau

Antonius J H Stegmann

Jorn Kaspers

Ronald Vogels

Stefan Kostense

Mieke Caroline Sprangers

Menzo Jans Emco Havenga

Menzo Havenga

Menzo J E Havenga

Guus Hateboer

Described are vaccines against malarial infections, which are based on recombinant viral vectors, such as alpha viruses, adenoviruses, or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against differentinfections, such as infections byor. Codon-optimized circumsporozoite genes are disclosed. Replication-defective adenoviruses may be used, derived from serotypes that encounter low titers of neutralizing antibodies. Also described is the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.

Recombinant viral-based malaria vaccines

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.

Settings for recombinant adenoviral-based vaccines

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.

The present invention relates to novel vaccines against malaria infections, based on recombinant viral vectors, such as alpha viruses, adenoviruses or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against differentinfections, such as infections byor. Novel codon-optimized circumsporozoite genes are disclosed. Preferably, replication-defective adenoviruses are used, derived from serotypes that encounter low titers of neutralizing antibodies. The invention, therefore, also relates to the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.

Described is a method for producing a protein of interest, the method comprising: a) providing a recombinant adenoviral vector comprising nucleic acid encoding the protein of interest under control of a promoter, wherein the adenoviral vector has deletions in a first region and in a second region of the adenovirus genome, wherein each of the first region and the second region is required for adenoviral genome replication and/or adenovirus particle formation, b) propagating the adenoviral vector in a first type of complementing cells that express proteins from the first and from the second region of the adenovirus genome so as to complement the deletions of the recombinant adenoviral vector, to obtain recombinant adenovirus particles, c) infecting a culture of a second type of complementing cells with the recombinant adenovirus particles, wherein the second type of complementing cells express protein from the first region of the adenovirus genome but not protein from the second region of the adenovirus genome, to produce the protein of interest, and d) harvesting the protein of interest.

Transient protein expression methods

The present invention relates to novel vaccines against malaria infections, based on recombinant viral vectors, such as alpha viruses, adenoviruses or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against differentinfections, such as infections byorNovel codon-optimized circumsporozoite genes are disclosed. Preferably, replication-defective adenoviruses are used, derived from serotypes that encounter low titers of neutralizing antibodies. The invention, therefore, also relates to the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.

Growing community of inventors

Zoetermeer, Netherlands

Lennart Holterman