Influenza virus vaccines and uses thereof
AssigneeIcahn School of Medicine at Mount Sinai
InventorsAdolfo GARCIA-SASTRE, Peter PALESE, Florian KRAMMER, Natalie PICA, Dirk EGGINK, Rafael A. MEDINA-SILVA, Rong HAI
Life of this patent
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Abstract
Provided herein are flu hemagglutinin polypeptides, including chimeric influenza virus hemagglutinin polypeptides, and flu hemagglutinin polypeptides comprising modified glycosylation sites and non-naturally glycosylation sites, compositions comprising the same, vaccines comprising the same and methods of their use.
Claims43
-85. (canceled)
A method for immunizing a subject against influenza virus disease or preventing influenza virus disease in a subject, comprising administering to the subject a first immunogenic composition comprising a first nucleic acid encoding a first chimeric influenza virus hemagglutinin (HA) polypeptide in an admixture with a first pharmaceutically acceptable carrier, wherein the first chimeric influenza virus HA polypeptide comprises a first HA stem domain and a first HA globular head domain, wherein the first HA globular head domain is from a different influenza A virus strain or subtype than the influenza A virus strain or subtype of the first HA stem domain, wherein the first nucleic acid is an RNA molecule comprising nucleotide analogs, and wherein the first pharmaceutically acceptable carrier comprises a biodegradable polymer, liposome, or micelle.
A method for immunizing a subject against influenza virus disease or preventing influenza virus disease in a subject, comprising administering to the subject an immunogenic composition comprising a chimeric influenza virus hemagglutinin (HA) polypeptide in an admixture with a pharmaceutically acceptable carrier, wherein the chimeric influenza virus HA polypeptide comprises an HA stem domain and an HA globular head domain, wherein the HA globular head domain is from a different influenza A virus strain or subtype than the influenza A virus strain or subtype of the HA stem domain, and wherein:
- (a) the HA stem domain comprises (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through Ap;
- and (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues Aq through HA1 C-term;
- and
- (b) the HA globular head domain comprises the amino acid residues between Ap and Aq of an HA1 domain;
- wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide;
- wherein HA1 C-term is the C-terminal amino acid of an HA1 domain;
- and wherein Ap is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering;
- and wherein Aq is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.
An influenza A virus comprising a chimeric influenza virus hemagglutinin (HA) polypeptide, wherein the chimeric influenza virus HA polypeptide comprises an HA stem domain and an HA globular head domain, wherein the HA globular head domain is from a different influenza A virus strain or subtype than the influenza A virus strain or subtype of the HA stem domain, and wherein:
- (a) the HA stem domain comprises (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through Ap;
- and (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues Aq through HA1 C-term;
- and
- (b) the HA globular head domain comprises the amino acid residues between Ap and Aq of an HA1 domain;
- wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide;
- wherein HA1 C-term is the C-terminal amino acid of an HA1 domain;
- and wherein Ap is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering;
- and wherein Aq is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.
Dependencies are inferred from the claim text.