Influenza nucleic acids, polypeptides, and uses thereof

Abstract

Codon-optimized nucleic acids encoding influenza polypeptides and uses of the nucleic acids and polypeptides for inducing immune responses are provided herein.

1 . An isolated nucleic acid molecule comprising:
 a sequence encoding an influenza type hemagglutinin (HA) polypeptide or antigenic fragment thereof, or an influenza neuraminidase (NA) polypeptide or antigenic fragment thereof, wherein the sequence has been codon-optimized for expression in a mammalian cell.   
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein the sequence encodes an influenza type A HA polypeptide selected from the following subtypes: H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, and H15. 
     
     
         3 . The nucleic acid molecule of  claim 1 , wherein the sequence encodes an HA polypeptide of the H1 subtype or the H3 subtype, and wherein the sequence is at least 90% identical to SEQ ID NO:1 or SEQ ID NO:3, or a fragment thereof containing at least 30 contiguous nucleotides of SEQ ID NO:1or SEQ ID NO:3. 
     
     
         4 . The nucleic acid molecule of  claim 1 , wherein the sequence further encodes a leader peptide that is not naturally associated with the influenza HA polypeptide. 
     
     
         5 . The nucleic acid molecule of  claim 1 , wherein the sequence encodes an extracellular portion of HA. 
     
     
         6 . The nucleic acid molecule of  claim 1 , wherein the sequence encodes an NA polypeptide, wherein the NA polypeptide is of the N2 subtype, and wherein the sequence is at least 90% identical to SEQ ID NO:5. 
     
     
         7 . A nucleic acid expression vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         8 . A composition comprising:
 (a) the nucleic acid molecule of  claim 1 ;   (b) a mammalian cytomegalovirus immediate-early promoter operably linked to the nucleic acid molecule, wherein the promoter directs transcription of mRNA encoding the influenza polypeptide; and   (c) a mammalian polyadenylation signal derived from a bovine growth hormone gene operably linked to the nucleic acid molecule.   
     
     
         9 . An isolated polypeptide encoded by the nucleic acid molecule of  claim 1 . 
     
     
         10 . An isolated antibody or antigen binding fragment thereof that specifically binds to a polypeptide of  claim 9 . 
     
     
         11 . A nucleic acid composition comprising:
 (a) a first sequence encoding a first type of influenza polypeptide of a first influenza subtype; and   (b) a second sequence encoding the first type of influenza polypeptide of a second influenza subtype.   
     
     
         12 . The nucleic acid composition of  claim 11 , wherein the first subtype is influenza A H1N1 and the second subtype is influenza A H3N2. 
     
     
         13 . The nucleic acid composition of  claim 11 , wherein one or both sequences have been codon-optimized for expression in a mammalian cell. 
     
     
         14 . The nucleic acid composition of  claim 13 , wherein the composition comprises a sequence at least 90% identical to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:5. 
     
     
         15 . The nucleic acid composition of  claim 11 , further comprising an influenza polypeptide. 
     
     
         16 . A nucleic acid composition comprising:
 (a) a first sequence encoding a first influenza polypeptide of a first influenza subtype; and   (b) a second sequence encoding a second influenza polypeptide of the first influenza subtype or a second influenza subtype;   wherein the sequence of (a) and the sequence of (b) have been codon-optimized for expression in a mammalian cell.   
     
     
         17 . The nucleic acid composition of  claim 16 , further comprising a sequence encoding a third influenza polypeptide. 
     
     
         18 . The nucleic acid composition of  claim 16 , wherein the first polypeptide is an influenza HA polypeptide comprising a sequence at least 90% identical to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:5. 
     
     
         19 . The nucleic acid composition of  claim 16 , further comprising an influenza polypeptide. 
     
     
         20 . A method for producing an influenza polypeptide, the method comprising:
 providing the nucleic acid molecule of  claim 1 ; and   expressing the nucleic acid in a host cell under conditions in which the influenza polypeptide encoded by the nucleic acid molecule is produced.