US2018333479A1PendingUtilityA1

Influenza virus vaccines and uses thereof

63
Assignee: ICAHN SCHOOL MED MOUNT SINAIPriority: Dec 18, 2012Filed: Apr 13, 2018Published: Nov 22, 2018
Est. expiryDec 18, 2032(~6.4 yrs left)· nominal 20-yr term from priority
Inventors:Adolfo Garcia-SastrePeter PaleseFlorian Krammer
A61P 31/16C12N 2760/16123A61K 2039/54A61K 2039/543C07K 14/005A61K 39/12C12N 2760/16223A61K 2039/545C12N 2760/16134C12N 2760/16234A61K 2039/55A61K 39/145A61K 2039/521A61K 2039/5252A61K 2039/70C12N 7/00
63
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Claims

Abstract

Provided herein are chimeric influenza hemagglutinin (HA) polypeptides, compositions comprising the same, vaccines comprising the same, and methods of their use.

Claims

exact text as granted — not AI-modified
1 .- 39 . (canceled) 
     
     
         40 . A method of immunizing a subject against influenza virus comprising administering to the subject an effective amount of an immunogenic composition comprising a first chimeric influenza virus hemagglutinin (HA) polypeptide and a second chimeric influenza virus HA polypeptide, wherein the first chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/Perth/16/2009 (H3N2) and a globular head of an influenza virus of an HA polypeptide of an influenza virus A/Duck/Czech/1956 (H4), and wherein the second chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/California/4/2009 (H1N1) and a globular head domain of an HA polypeptide of an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5). 
     
     
         41 - 43 . (canceled) 
     
     
         44 . A method of preventing an influenza virus disease in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a first chimeric influenza virus hemagglutinin (HA) polypeptide and a second chimeric influenza virus HA polypeptide, wherein the first chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/Perth/16/2009 (H3N2) and a globular head of an influenza virus of the HA polypeptide of an influenza virus A/Duck/Czech/1956 (H4), and wherein the second chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/California/4/2009 (H1N1) and a globular head domain of an HA polypeptide of an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5). 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 40 , wherein the subject is a human. 
     
     
         47 - 48 . (canceled) 
     
     
         49 . The method of  claim 40 , wherein the immunogenic composition is administered intramuscularly or intranasally to the subject. 
     
     
         50 - 65 . (canceled) 
     
     
         66 . A method of immunizing a subject against influenza virus comprising administering to the subject an effective amount of an immunogenic composition comprising a first influenza A virus and a second influenza A virus, wherein the first influenza A virus comprises a first chimeric influenza virus hemagglutinin (HA) polypeptide and the second influenza A virus comprises a second chimeric influenza virus HA polypeptide, wherein the first chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/Perth/16/2009 (H3N2) and a globular head of an influenza virus of the HA polypeptide of an influenza virus A/Duck/Czech/1956 (H4), and wherein the second chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/California/4/2009 (H1N1) and a globular head domain of an HA polypeptide of an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5). 
     
     
         67 . A method of preventing an influenza virus disease in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a first influenza A virus and a second influenza A virus, wherein the first influenza A virus comprises a first chimeric influenza virus hemagglutinin (HA) polypeptide and the second influenza A virus comprises a second chimeric influenza virus HA polypeptide, wherein the first chimeric influenza virus HA polypeptide comprises a stem domain of an HA polypeptide of an influenza virus A/Perth/16/2009 (H3N2) and a globular head of an influenza virus of an HA polypeptide of an influenza virus A/Duck/Czech/1956 (H4), and wherein the second chimeric influenza virus HA polypeptide comprises a stem domain of an HA of an influenza virus A/California/4/2009 (H1N1) and a globular head domain of an HA polypeptide of an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5). 
     
     
         68 . The method of  claim 40 , wherein
 (a) the HA stem domain of the first and second chimeric influenza virus HA polypeptide each comprise (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term  through A p ; (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q  through HA1 C-term ; and (iii) an HA2 stem domain; and   (b) the HA globular head domain of the first and second chimeric influenza virus HA polypeptide each comprise the amino acid residues between A p  and A q  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 A p  is a Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q  is a Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering. 
   
     
     
         69 . The method of  claim 44 , wherein
 (a) the HA stem domain of the first and second chimeric influenza virus HA polypeptide each comprise (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term  through A p ; (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q  through HA1 C-term ; and (iii) an HA2 stem domain; and   (b) the HA globular head domain of the first and second chimeric influenza virus HA polypeptide each comprise the amino acid residues between A p  and A q  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 A p  is a Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q  is a Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering. 
   
     
     
         70 . The method of  claim 66 , wherein
 (a) the HA stem domain of the first and second chimeric influenza virus HA polypeptide each comprise (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term  through A p ; (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q  through HA1 C-term ; and (iii) an HA2 stem domain; and   (b) the HA globular head domain of the first and second chimeric influenza virus HA polypeptide each comprise the amino acid residues between A p  and A q  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 A p  is a Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q  is a Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering. 
   
     
     
         71 . The method of  claim 67 , wherein
 (a) the HA stem domain of the first and second chimeric influenza virus HA polypeptide each comprise (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term  through A p ; (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q  through HA1 C-term ; and (iii) an HA2 stem domain; and   (b) the HA globular head domain of the first and second chimeric influenza virus HA polypeptide each comprise the amino acid residues between A p  and A q  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 A p  is a Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q  is a Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering. 
   
     
     
         72 . The method of  claim 68 , wherein the first chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/Perth/16/2009 (H3N2), and wherein the second chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/California/4/2009 (H1N1). 
     
     
         73 . The method of  claim 69 , wherein the first chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/Perth/16/2009 (H3N2), and wherein the second chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/California/4/2009 (H1N1). 
     
     
         74 . The method of  claim 70 , wherein the first chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/Perth/16/2009 (H3N2), and wherein the second chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/California/4/2009 (H1N1). 
     
     
         75 . The method of  claim 71 , wherein the first chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/Perth/16/2009 (H3N2), and wherein the second chimeric influenza virus HA polypeptide comprises transmembrane and cytoplasmic domains of the HA polypeptide of influenza virus A/California/4/2009 (H1N1). 
     
     
         76 . The method of  claim 44 , wherein the subject is a human. 
     
     
         77 . The method of  claim 66 , wherein the subject is a human. 
     
     
         78 . The method of  claim 67 , wherein the subject is a human. 
     
     
         79 . The method of  claim 44 , wherein the immunogenic composition is administered intramuscularly or intranasally to the subject. 
     
     
         80 . The method of  claim 66 , wherein the immunogenic composition is administered intramuscularly or intranasally to the subject. 
     
     
         81 . The method of  claim 67 , wherein the immunogenic composition is administered intramuscularly or intranasally to the subject. 
     
     
         82 . The method of  claim 66 , wherein the first and second influenza A viruses are inactivated. 
     
     
         83 . The method of  claim 67 , wherein the first and second influenza A viruses are inactivated. 
     
     
         84 . The method of  claim 72 , wherein the subject is a human. 
     
     
         85 . The method of  claim 73 , wherein the subject is a human. 
     
     
         86 . The method of  claim 74 , wherein the subject is a human. 
     
     
         87 . The method of  claim 75 , wherein the subject is a human. 
     
     
         88 . The method of  claim 40 , wherein the immunogenic composition is a subunit vaccine. 
     
     
         89 . The method of  claim 44 , wherein the immunogenic composition is a subunit vaccine. 
     
     
         90 . The method of  claim 66 , wherein the immunogenic composition is a split vaccine. 
     
     
         91 . The method of  claim 67 , wherein the immunogenic composition is a split vaccine.

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