Influenza virus vaccines and uses thereof
AssigneeIcahn School of Medicine at Mount Sinai
InventorsAdolfo Garcia-Sastre, Anice C. Lowen, Peter Palese, John Steel
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Abstract
Provided herein are influenza hemagglutinin stem domain polypeptides, compositions comprising the same, vaccines comprising the same and methods of their use.
Claims29
A method of inducing an immune response to an influenza virus hemagglutinin (HA) in a subject comprising administering to a subject a vaccine comprising a polypeptide, wherein said polypeptide comprises:
- (a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1 to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal stem segment;
- said HA1 domain in tertiary or quaternary association with
- (b) an influenza hemagglutinin HA2 domain,
- wherein the vaccine induces antibodies which are cross-reactive among HA subtypes, and wherein said polypeptide comprises a disulfide bridge between Ap and Aq, wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering and Aq is Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.
A method of inducing an immune response to an influenza virus hemagglutinin (HA) in a subject comprising administering to a subject a vaccine comprising a nucleic acid encoding a polypeptide, wherein said polypeptide comprises:
- (a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1 to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal stem segment;
- said HA1 domain in tertiary or quaternary association with
- (b) an influenza hemagglutinin HA2 domain,
- wherein the vaccine induces antibodies which are cross-reactive among HA subtypes,
- and wherein said polypeptide comprises a disulfide bridge between Ap and Aq, wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering and Aq is Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.
A method of inducing an immune response to an influenza virus hemagglutinin (HA) in a subject comprising administering to a subject a vaccine comprising a virus comprising a polypeptide, wherein said polypeptide comprises:
- (a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1 to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal stem segment;
- said HA1 domain in tertiary or quaternary association with
- (b) an influenza hemagglutinin HA2 domain,
- wherein the vaccine induces antibodies which are cross-reactive among HA subtypes,
- and wherein said polypeptide comprises a disulfide bridge between Ap and Aq, wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering and Aq is Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.
Dependencies are inferred from the claim text.