Crucell Holland B.v.

Janssen Vaccines & Prevention B.v.

Aeras Global Tb Vaccine Foundation

Massachusetts Institute of Technology

Galapagos Genomics N.v.

Introgene B.v.

Galapagos Geonomics N.v.

Ronald Vogels

Abraham Bout

Menzo Jans Emco Havenga

Menzo Havenga

Majid Mehtali

David Adrianus Theodorus Maria Zuijdgeest

Katarina Radosevic

Menzo J E Havenga

Robert Heinz Edward Friesen

Govert Johan Schouten

Lennart Holterman

Jerald C Sadoff

Maria Grazia Pau

David M Hone

Joost Alexander Kolkman

Theodorus H J Kwaks

Boerries Brandenburg

Robert H E Friesen

Stefan Kostense

Mieke Caroline Sprangers

Darrell J Irvine

Ron Weiss

Ely Blanton Porter

Theodorus Hendrikus Jacobus Kwaks

Antonietta Impagliazzo

Stefan Loverix

Jan Willem Meijberg

Mariane Bandeira Melo

Tasuku Kitada

Marijn Van Der Neut Kolfschoten

Helmuth Van Es

Philippe Alard

Yasir Abdul Wahid Skeiky

Yasir A W Skeiky

Guus Hateboer

Jaroslaw Juraszek

Helmuth H G Van Es

Govert Shouten

Theodorus Hendrikus Kwaks

Davide Branduardi

Jan Wilem Meijberg

David ATM Zuijdgeest

Menzo Jans Emko Havenga

Compositions and methods are described for inducing an immune response against an immunogen in humans. The induced immune response is obtained by administering a heterologous prime-boost combination of an in vitro transcribed (IVT) self-replicating RNA (repRNA) and an adenovirus vector. The compositions and methods can be used to provide a protective immunity against a disease, such as a viral infection or a cancer, in humans.

Methods and compositions for heterologous repRNA immunizations

A method of designing a D-polypeptide that binds with an L-target protein can include: identifying a polypeptide target having L-chirality; determining hotspot amino acids of a polypeptide ligand having L-chirality that have binding interactions with the L-target protein; determining transformations of side chains of the hotspot amino acids that retain the binding interactions with the target; generating inversed hotspot amino acids with chirality opposite to the one of the target; identifying a polypeptide having inverse chirality from the target protein, on which a combination of inversed hotspot amino-acid can be grafted without significantly changing their interactions with the target. The designed ligands can be processed and converted to D-ligands that bind with the L-target protein.

Structure based design of d-protein ligands

Multimeric binding molecules that are capable of specifically binding to hemagglutinin (HA) of at least two influenza A virus strains, said strains comprising HA of two different HA subtypes from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza B virus strain are provided. The binding molecules preferably are also capable of neutralizing at least two influenza A virus strains from phylogenetic group 2; or capable of neutralizing at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically neutralizing at least one influenza B virus strain.

Binding molecules directed against influenza hemagglutinin and uses thereof

Monomeric and multimeric binding molecules that are capable of specifically binding to hemagglutinin (HA) of at least two influenza A virus strains, said strains including HA of two different HA subtypes from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza B virus strain are provided. The binding molecules preferably are also capable of neutralizing at least two influenza A virus strains from phylogenetic group 2; or capable of neutralizing at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically neutralizing at least one influenza B virus strain.

The present disclosure provides influenza hemagglutinin stem domain polypeptides comprising (a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment, covalently linked by a linking sequence of 0-50 amino acid residues to an HA1 C-terminal stem segment, and (b) an influenza hemagglutinin HA2 domain, wherein on or more amino acids in the HA2 domain have been mutated. Also provided are nucleic acids encoding the polypeptides, compositions comprising the polypeptides and/or nucleic acid molecules, as well as methods of their use, in particular in the detection, prevention and/or treatment of influenza.

Influenza virus vaccines and uses thereof

Described are binding molecules, such as human monoclonal antibodies, that bind to an epitope in the stem region of hemagglutinin of influenza A viruses of phylogenetic group 1 and group 2, as well as influenza B viruses, and have a broad neutralizing activity against such influenza viruses. Provided are nucleic acid molecules encoding the binding molecules, their sequences, and compositions comprising the binding molecules. The binding molecules can be used, for example, in the diagnosis, prophylaxis, and/or treatment of influenza A viruses of phylogenetic groups 1 and 2, as well as influenza B viruses.

Human binding molecules capable of neutralizing influenza A viruses of phylogenetic group 1 and phylogenetic group 2 and influenza B viruses

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&#xae; 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. Also, the cell lines are useful for producing human viruses other than adenovirus such as influenza virus, herpes simplex virus, rotavirus, and measles virus.

Complementing cell lines

Described are binding molecules, such as human monoclonal antibodies, that bind to hemagglutinin of influenza B viruses, and have a broad neutralizing activity against such influenza viruses. These binding molecules do not bind to hemagglutinin of influenza A viruses. Further provided are nucleic acid molecules encoding the binding molecules, and compositions comprising the binding molecules. The binding molecules can be used in the diagnosis of, prophylaxis against, and/or treatment of influenza B virus infections.

Human binding molecules capable of binding to and neutralizing influenza B viruses and uses thereof

The present disclosure relates to binding molecules, such as human monoclonal antibodies, that bind to an epitope in the stem region of hemagglutinin of influenza A viruses of phylogenetic group 1 and group 2, as well as influenza B viruses, and have a broad neutralizing activity against such influenza viruses. The disclosure provides nucleic acid molecules encoding the binding molecules, their sequences and compositions comprising the binding molecules. The binding molecules can be used in the diagnosis, prophylaxis and/or treatment of influenza A viruses of phylogenetic groups 1 and 2, as well as influenza B viruses.

Growing community of inventors

Linschoten, Netherlands

Ronald Vogels