Bavarian Nordic A/s

Hubertus Hochrein

Meredith O'Keeffe

Jürgen Hausmann

Robin Steigerwald

Stefan Bauer

Henning Lauterbach

Ulrike Dirmeier

Ariane Volkmann

José Medina Echeverz

Matthias Habjan

Meredith O'keeffe

Christine Meisinger-Henschel

Carsten Juergen Kirschning

Stephanie Sanos

Juergen Hausmann

Jurgen Hausmann

Meredith O'KEEFFE

Carsten Kirschning

The invention relates to a pharmaceutical combination and related methods for reducing tumor volume and/or increasing the survival of a cancer patient. The combination comprises an intravenous administration of a recombinant MVA encoding a tumor-associated antigen and an administration of an antibody to a cancer patient.

Combination therapy for treating cancer with an antibody and intravenous administration of a recombinant MVA

The present invention relates to an improved filovirus vaccine comprising a recombinant modified vaccinia virus Ankara-based (MVA-based) vaccine against filovirus infection and to related products, methods and uses. Specifically, the present invention relates to genetically engineered (recombinant) MVA and FPV vectors comprising at least one heterologous nucleotide sequence encoding an antigenic determinant of a Marburg virus (MARV) or Ebola virus glycoprotein. Specifically, the invention relates to recombinant MVA comprising Ebola virus glycoprotein and virion protein 40. The invention also relates to products, methods and uses thereof as well as prime/boost regimens of MVA and genetically engineered (recombinant) FPV, e.g., suitable to induce a protective immune response in a subject.

Multivalent recombinant modified vaccinia virus ankara (MVA) vector encoding filovirus immunogens

Combination therapy for treating cancer with an intravenous administration of a recombinant MVA and an antibody

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.

Methods and compositions for enhancing vaccine immune responses

Recombinant modified vaccinia virus Ankara (MVA) multivalent filovirus immunogenic compositions and methods of use

Provided herein are immunogenic compositions comprising a recombinant modified vaccinia virus Ankara (MVA) comprising a nucleic acid sequence encoding a flagellin, and a nucleic acid sequence encoding a heterologous disease-associated antigen, wherein the immunogenic composition induces increased T-cell and antibody mediated immune responses specific for the heterologous disease-associated antigen when administered to a subject, e.g. a human subject, and related methods and uses.

Methods and compositions for intra-nasal immunization with recombinant MVA encoding flagellin

The present invention relates to the field of immunology. The present invention provides agonists and antagonists of Toll-like receptor (TLR) 13. In particular, the present invention provides TLR13 activating and inhibiting nucleic acids, and provides such nucleic acids for use as pharmaceutical agents. The present invention further provides in vitro methods using such nucleic acids.

Agonists and antagonists of toll-like receptor (TLR) 13

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.

Interferon-alpha-producing bone marrow dendritic cells

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-&#x3bb;) 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-&#x3bb; and/or generating or obtaining a population of IFN-&#x3bb; 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.

Production of IFN-lambda by conventional dendritic cells

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.

Immediate protection against pathogens via MVA

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.

Modulation of immune responses by the poxviral K4 protein

A method of inducing dendritic cell (DC) development by administering Macrophage-Colony Stimulating Factor (M-CSF) is provided. M-CSF induces DCs to differentiate into Subtypes, for example plasmacytoid DCs and conventional DCs. Said differentiation is independent of Fms-like-Tyrosine-Kinase 3-Ligand (FL) and/or Granulocyte-Macrophage-Colony Stimulating Factor (GM-CSF). Induction with M-CSF can be achieved in vitro from hematopoietic precursors, such as bone marrow cells, or in vivo. In vitro, M-CSF-derived DCs can be used to produce cytokines and to stimulate other immune response cells. M-CSF can also be used to induce precursor cells removed from an animal to develop into DCs. In addition, these isolated DCs can be exposed to antigens to stimulate a specific immune response when reintroduced into the animal. Treatments for Cancers, such as Acute Myeloid Leukemia, and autoimmune diseases such as Systemic Lupus Erythematosus, are also provided in the invention.

Induction of dendritic cell development with macrophage-colony stimulating factor (M-CSF)

A method of inducing dendritic cell (DC) development by administering Macrophage-Colony Stimulating Factor is provided. M-CSF induces DCs to differentiate into subtypes, for example plasmacytoid DCs and conventional DCs. Induction with M-CSF can be achieved in vitro from hematopoietic precursors, such as bone marrow cells, or in vivo. In vitro, M-CSF-derived DCs can be used to produce cytokines and to stimulate other immune response cells. M-CSF can also be used to induce precursor cells removed from an animal to develop into DCs. In addition, these isolated DCs can be exposed to antigens to stimulate a specific immune response when reintroduced into the animal. Treatments for cancers, such as Acute Myeloid Leukemia, and autoimmune diseases such as Systemic Lupus Erythematosus, are also provided in the invention.

The invention relates to the methods and kits comprising modified vaccinia virus Ankara (MVA) to provide immediate protection against pathogens. MVA can be delivered to a host animal just prior to or after exposure to a pathogen and provide protection against the pathogen.

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Munich, Germany

Hubertus Hochrein