Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: RNA replicons encoding stabilized recombinant pre-fusion SARS CoV-2 S proteins are described. Also described are pharmaceutical compositions and uses of the RNA replicons.

Abstract: RNA replicons encoding coronavirus S proteins, in particular SARS-CoV-2 S proteins, are described. Also described are pharmaceutical compositions and uses of the RNA replicons.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.