Influenza nucleic acid molecules and vaccines made therefrom

Abstract

Provided herein are nucleic acid sequences that encode novel consensus amino acid sequences of HA hemagglutinin and/or influenza B hemagglutinin, as well as genetic constructs/vectors and vaccines expressing the sequences. Also provided herein are methods for generating an immune response against one or more influenza A serotypes and/or influenza B serotypes, or combinations thereof, using the vaccines that are provided.

1 . A multiple consensus subtype vaccine wherein the vaccine provides cross-reactivity against a variety of influenza strains, the vaccine comprising at least one consensus hemagglutinin antigen. 
     
     
         2 . The vaccine of  claim 1 , wherein the consensus hemagglutinin antigen is selected from the group consisting of H1 hemagglutinin, H2 hemagluttinin, H3 hemagglutinin, and influenza B hemagglutinin, and any combination thereof. 
     
     
         3 . The vaccine of  claim 2 , wherein the H1 hemagglutinin is selected from the group consisting of HS09, H1Bris, H1TT, H1U, and any combination thereof. 
     
     
         4 . The vaccine of  claim 2 , wherein the H3 hemagglutinin is selected from the group consisting of H3HA-1, H3HA-2, and any combination thereof. 
     
     
         5 . The vaccine of  claim 2 , wherein the influenza B hemagglutinin is selected from the group consisting of BHA-1, BHA-2, and any combination thereof. 
     
     
         6 . The vaccine of  claim 3 , wherein HS09 comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:2, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:2; a fragment of nucleic acid sequences encoding SEQ ID NO:2; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:2;
 wherein H1Bris comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:20, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:20; a fragment of nucleic acid sequences encoding SEQ ID NO:20; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:20;   wherein H1TT comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:22, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:22; a fragment of nucleic acid sequences encoding SEQ ID NO:22; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:22;   wherein H1U comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:36, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:36; a fragment of nucleic acid sequences encoding SEQ ID NO:36; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:36.   
     
     
         7 . The vaccine of  claim 3 , wherein H509 comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:1; a fragment of SEQ ID NO:1; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:1;
 wherein H1Bris comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:19, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:19; a fragment of SEQ ID NO:19; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:19;   wherein H1TT comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:21, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:21; a fragment of SEQ ID NO:21; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:21; and   wherein H1U comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:35, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:35; a fragment of SEQ ID NO:35; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:35.   
     
     
         8 . The vaccine of  claim 4 , wherein H3HA-1 comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:38, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:38; a fragment of nucleic acid sequences encoding SEQ ID NO:38; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:38;
 wherein H3HA-2 comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:24, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:24; a fragment of nucleic acid sequences encoding SEQ ID NO:24; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:24.   
     
     
         9 . The vaccine of  claim 4 , wherein H3HA-1 comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:37, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:37; a fragment of SEQ ID NO:37; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:37;
 wherein H3HA-2 comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:23, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:23; a fragment of SEQ ID NO:23; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:23.   
     
     
         10 . The vaccine of  claim 5 , wherein BHA-1 comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:14, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:14; a fragment of nucleic acid sequences encoding SEQ ID NO:14; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:14;
 wherein BHA-2 comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding SEQ ID NO:26, a nucleic acid sequence that is at least 95% homologous to nucleic acid sequences encoding SEQ ID NO:26; a fragment of nucleic acid sequences encoding SEQ ID NO:26; a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding SEQ ID NO:26.   
     
     
         11 . The vaccine of  claim 5 , wherein BHA-1 comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:13, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:13; a fragment of SEQ ID NO:13; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:13;
 wherein BHA-2 comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:25, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:25; a fragment of SEQ ID NO:25; a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:25.   
     
     
         12 . A method of inducing cross-reactivity against a variety of influenza strains in a mammal, the method comprising administering to the mammal in need thereof the vaccine of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein each of the consensus hemagglutinin antigen is administered to the mammal separately. 
     
     
         14 . The method of  claim 12 , wherein each of the consensus hemagglutinin antigen is administered to the mammal simultaneously. 
     
     
         15 . An isolated nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:2, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:20, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:22, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:36, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:38, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:24, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:14, a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:26,   a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:2, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:20, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:22, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:36, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:38, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:24, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:14, a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:26,   a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:2, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:20, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:22, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:36, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:38, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:24, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:14, a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:26,   a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:2, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:20, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:22, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:36, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:38, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:24, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:14, a nucleic acid sequence that is at least 95% homologous to a fragment of nucleic acid sequences encoding the amino acid sequence of SEQ ID NO:26.   
     
     
         16 . The isolated nucleic acid molecule of  claim 1  comprising one or more nucleic acid sequences selected from the group consisting of:
 SEQ ID NO:1, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:23, SEQ ID NO:13, SEQ ID NO:25, 
 a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:1, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:19, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:21, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:35, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:37, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:23, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:13, a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:25, 
 a fragment of SEQ ID NO:1, a fragment of SEQ ID NO:19, a fragment of SEQ ID NO:21, a fragment of SEQ ID NO:35, a fragment of SEQ ID NO:37, a fragment of SEQ ID NO:23, a fragment of SEQ ID NO:13, a fragment of SEQ ID NO:25, 
 a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:1, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:19, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:21, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:35, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:37, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:23, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:13, a nucleic acid sequence that is at least 95% homologous to a fragment of SEQ ID NO:25. 
 
     
     
         17 . An expression vector comprising a nucleic acid sequence of  claim 15  operably linked to regulatory element. 
     
     
         18 . A composition comprising a first and second nucleic acid sequence, wherein the first nucleic acid sequence comprises a sequence of  claim 15 ,
 and wherein the second nucleic acid sequence comprises one or more nucleic acid sequence that encodes a protein selected from the group consisting of one or more of: influenza A H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, N1, N2, N3, N4, N5, N6, N7, N8, N9, influenza B hemagglutinin, neuraminidase, and a fragment thereof.   
     
     
         19 . A composition comprising a first and second nucleic acid sequence, wherein the first nucleic acid sequence comprises a sequence of  claim 16 ,
 and wherein the second nucleic acid sequence comprises one or more nucleic acid sequence that encodes a protein selected from the group consisting of one or more of: influenza A H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, N1, N2, N3, N4, N5, N6, N7, N8, N9, influenza B hemagglutinin, neuraminidase, and a fragment thereof.   
     
     
         20 . A method of inducing an immune response in a mammal comprising administering to the mammal a nucleic acid sequence of  claim 15 .