Abstract: A novel dendritic cell type has been identified within bone marrow, termed myelos interferon dendritic cells (miDC). These novel cells possess the high IFN-alpha producing activity of pDC, but they also display a wide TLR responsiveness along with T-cell stimulation capacities that more closely resemble the conventional DC populations. Moreover, these cells appear less prone to apoptosis upon activation stimuli, including viruses. These cells constitute a novel bone marrow innate immune cell type, ideally geared to linking innate and adaptive immune responses via their potent IFN-alpha production and high cell stimulatory capacity.

Abstract: The present invention relates to methods for purification of Vaccinia viruses (VV) and/or Vaccinia virus (VV) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

Abstract: The present invention relates to a recombinant poxvirus vector capable of expressing two or more homologous, foreign sequences, which derive from different variants of a microorganism, and which have a homology of 50% or above. The invention further relates to a method for preparing such recombinant poxvirus and the use of such recombinant poxvirus as medicament or vaccine. Additionally, a method for affecting preferably inducing, an immune response in a living animal, including a human, is provided.

Abstract: Provided herein are recombinant modified vaccinia virus Ankara (MVA) strains as improved vaccines against infection with Respiratory Syncytial Virus (RSV virus) and to related products, methods and uses. Specifically, provided herein are genetically engineered recombinant MVA vectors comprising at least one nucleotide sequence encoding an antigenic determinant of an RSV membrane glycoprotein and at least one nucleotide sequence encoding an antigenic determinant of an RSV nucleocapsid protein. Also provided herein are products, methods and uses thereof, e.g., suitable to affect an immune response in a subject, or suitable to diagnose an RSV infection, as well as to determine whether a subject is at risk of recurrent RSV infection.

Abstract: In the present invention, CD8+ conventional dendritic cells (CD8+ cDCs) and equivalents thereof (eCD8+ cDCs) in mouse and human have been established as major source of IFN-lambda (IFN-?) in response to double-stranded (ds) nucleic acids. The invention relates to therapeutic applications of ds nucleic acids or analogs thereof targeting CD8+ and/or eCD8+ cDCs in the prevention and/or treatment of infectious diseases, preferably viral infections, or cancer. Furthermore, the invention relates to an in vitro method for producing IFN-? and/or generating or obtaining a population of IFN-? producing CD8+ or eCD8+ cDCs as well as in vitro method for detecting or screening for CD8+ and/or eCD8+ cDCs. In addition, the invention relates to a Flt3-ligand or a M-CSF receptor ligand for use in increasing the level of CD8+ and/or eCD8+ cDCs in a subject suffering from an infectious disease or cancer.

Abstract: Provided herein are immunogenic compositions comprising a recombinant modified vaccinia virus Ankara (MVA) comprising a nucleic acid sequence encoding a CD40 ligand (CD40L) and a nucleic acid sequence encoding a heterologous disease-associated antigen, wherein the immunogenic composition induces increases T-cell immune responses specific for the heterologous disease-associated antigen when administered to a human host, and related methods and uses.

Abstract: The invention is drawn to compositions and methods for the induction of an immune response, in particular a strong CD8 T cell response, to a specific antigenic determinant without raising a significant antibody response to the antigenic determinant after a first, priming immunization. The method comprises administering to the host a recombinant poxviral vector comprising a transcriptional control element comprising an early and/or late element linked to a nucleotide sequence encoding the antigenic determinant. The recombinant poxviral vector comprises a transcriptional control element comprising an early and/or late element linked to a nucleotide sequence encoding the antigenic determinant. The late element may be stronger than the cowpox ATI promoter in HeLa cells.

Abstract: The invention relates to vectors comprising two or more homologous nucleotide sequences and methods for generating them. The invention concerns substituting bases in the homologous nucleotide sequences with different bases that do not alter the encoded amino acid sequence. The invention allows for the reduction of intramolecular recombination between homologous nucleotide sequences, in particular in mammalian cells. The invention further relates to nucleotide sequences containing substituted bases.

Abstract: The invention relates to methods and kits comprising poxviruses including, but not limited to modified vaccinia virus Ankara (MVA) and uses thereof to provide immediate protection against pathogens. Poxviruses including, but not limited to MVA can be delivered to a host animal just prior to or after exposure to a pathogen and provide protection against the pathogen.

Abstract: The present invention relates to the rapid induction of a protective immune response against infectious agents using a poxvirus. An immune response can be induced by administering the poxvirus 7 to 2 days prior to infection with the infections agents.

Abstract: The invention relates to a promoter selected from a group of nucleic acids consisting of: (a) A nucleic acid having a nucleotide sequence as set out in SEQ ID NO: 1; (b) A nucleic acid having a nucleotide sequence derived from the nucleic acid set out in (a), comprising at least one nucleotide addition, deletion, substitution and/or inversion as compared to the nucleotide sequence of (a) and having essentially the same expression characteristics as the nucleic acid of (a); (c) A nucleic acid sequence having at least 70% identity with the nucleic acid of (a) and having essentially the same expression characteristics as the nucleic acid of (a); and (d) A nucleic acid capable of hybridizing to a nucleic acid of (a), (b) or (c) and having essentially the same expression characteristics as the nucleic acid of (a).

Abstract: The present invention relates to compositions, methods, and uses involving the modulation of K4 protein activity, especially in the treatment of various diseases and in the enhancement of vaccination regimens. The invention relates to poxviruses having reduced or increased K4 protein activity, as well as methods of making and using these poxviruses. The invention further relates to K4 proteins and inhibitors of K4 protein activity, as well as methods for making and using them.

Abstract: The present invention provides modified vaccinia virus (VACV) genomes as well as vectors, especially viral vectors comprising the same. The present invention further provides modified vaccinia viruses. The present invention further provides methods for determining the effect of mutations in VACV with regard to competence for replication in certain cell types. The present invention further provides methods of preparing modified vaccinia viruses.

Abstract: The present invention relates to NS1 proteins or parts thereof of Flaviviruses, in particular of Dengue viruses useful for vaccination against said Flavivirus and against one or more other Flaviviruses. The invention further concerns the NS1 protein or parts thereof of one Dengue virus serotype, in particular serotype 2, useful for vaccination against Dengue viruses from all serotypes. The invention further concerns DNA comprising an expression cassette coding for a Flavivirus NS1 or parts thereof, vectors comprising said DNA and vaccines containing or expressing a Flavivirus NS1.

Abstract: The present invention relates to the rapid induction of a protective immune response against infectious agents using a poxvirus. An immune response can be induced by administering the poxvirus 7 to 2 days prior to infection with the infections agents.

Abstract: The invention relates to a promoter selected from a group of nucleic acids consisting of (a) a nucleic acid having the nucleotide sequence of SEQ ID NO:1; (b) a nucleic acid having a nucleotide sequence derived from SEQ ID NO:1, wherein not more than 10 nucleotides have been added, deleted, substituted and/or inverted from the nucleic acid of SEQ ID NO:1; and (c) a nucleic acid sequence having at least 70% identity with the nucleic acid of (a); wherein the promoter has a length of up to and including 27 nucleotides and wherein the promoter according to options (b) and (c) exhibits at least the 70% of the promoter activity of SEQ ID NO:1 as measured by the amount of recombinant protein produced.

Abstract: The present invention relates to novel insertion sites useful for the integration of exogenous sequences into the Modified Vaccinia Ankara (MVA) virus genome. The present invention further provides plasmid vectors to insert exogenous DNA into the genome of MVA. Furthermore, the present invention provides recombinant MVA comprising an exogenous DNA sequence inserted into the new insertion site as medicine or vaccine.

Abstract: The present invention relates to a replication deficient recombinant virus encoding at least one antigen and/or antigenic epitope, wherein expression of said antigen and/or antigenic epitope is regulated by a transcriptional control element comprising at least two elements driving early expression of said antigen and/or antigenic epitope and the use of said replication deficient recombinant virus as medicament or vaccine.

Abstract: The present invention relates to a method for the cultivation of primary cells. The primary cells are cultivated in a serum free medium comprising a factor selected from the group consisting of growth factors and attachment factors. The method for the cultivation of primary cells may be one step in a method for the amplification of viruses, such as poxviruses. According to this latter method the primary cells are cultivated in a serum free medium comprising a factor selected from the group consisting of growth factors and attachment factors. The cells are then infected with the virus and the infected cells are cultivated in serum free medium until progeny virus is produced.

Abstract: The present invention relates to a replication deficient recombinant virus encoding at least one antigen and/or antigenic epitope, wherein expression of said antigen and/or antigenic epitope is regulated by a transcriptional control element comprising at least two elements driving early expression of said antigen and/or antigenic epitope and the use of said replication deficient recombinant virus as medicament or vaccine.