Novel Vaccines Against Multiple Subtypes of Influenza Virus

Abstract

An aspect of the present invention is directed towards DNA plasmid vaccines capable of generating in a mammal an immune response against a plurality of influenza virus subtypes, comprising a DNA plasmid and a pharmaceutically acceptable excipient. The DNA plasmid is capable of expressing a consensus influenza antigen in a cell of the mammal in a quantity effective to elicit an immune response in the mammal, wherein the consensus influenza antigen comprises consensus hemagglutinin (HA), neuraminidase (NA), matrix protein, nucleoprotein, M2 ectodomain-nucleo-protein (M2e-NP), or a combination thereof. Preferably the consensus influenza antigen comprises HA, NA, M2e-NP, or a combination thereof. The DNA plasmid comprises a promoter operably linked to a coding sequence that encodes the consensus influenza antigen. Additionally, an aspect of the present invention includes methods of eliciting an immune response against a plurality of influenza virus subtypes in a mammal using the DNA plasmid vaccines provided.

1 - 53 . (canceled) 
     
     
         54 . A composition for inducing an immune response against influenza, comprising one or more nucleotide sequences selected from the group consisting of:
 a) a nucleotide sequence encoding a consensus neuraminidase (NA) antigen, and   b) a nucleotide sequence encoding a consensus M2 ectodomain-nucleoprotein (M2e-NP) antigen .   
     
     
         55 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus NA antigen is selected from the group consisting of: a nucleotide sequence encoding SEQ ID NO: 4, a nucleotide sequence encoding an amino acid sequence having at least 90% homology to SEQ ID NO: 4, and a fragment of a nucleotide sequence encoding SEQ ID NO: 4. 56 (New) The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus NA antigen encodes an amino acid sequence having at least 90% homology to SEQ ID NO: 4. 
     
     
         57 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus NA antigen encodes an amino acid sequence comprising SEQ ID NO: 4. 
     
     
         58 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus NA antigen is selected from the group consisting of: a nucleotide sequence comprising SEQ ID NO: 3, a nucleotide sequence having at least 90% homology to SEQ ID NO: 3, and a fragment of a nucleotide sequence comprising SEQ ID NO: 3. 
     
     
         59 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus NA antigen comprises a nucleotide sequence having at least 90% homology to SEQ ID NO: 3. 
     
     
         60 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus NA antigen comprises SEQ ID NO:3. 
     
     
         61 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus M2e-NP antigen is selected from the group consisting of: a nucleotide sequence encoding SEQ ID NO: 8, a nucleotide sequence encoding an amino acid sequence having at least 90% homology to SEQ ID NO: 8, and a fragment of a nucleotide sequence encoding SEQ ID NO: 8. 
     
     
         62 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus M2e-NP antigen encodes an amino acid sequence having at least 90% homology to SEQ ID NO: 8. 
     
     
         63 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus M2e-NP antigen encodes an amino acid sequence comprising SEQ ID NO: 8. 
     
     
         64 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus M2e-NP antigen is selected from the group consisting of: a nucleotide sequence comprising SEQ ID NO: 7, a nucleotide sequence having at least 90% homology to SEQ ID NO: 7, and a fragment of a nucleotide sequence comprising SEQ ID NO: 7. 
     
     
         65 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus M2e-NP antigen comprises a nucleotide sequence having at least 90% homology to SEQ ID NO: 7. 
     
     
         66 . The composition of  claim 54 , wherein the nucleotide sequence encoding the consensus M2e-NP antigen comprises SEQ ID NO: 7. 
     
     
         67 . The composition of  claim 54 , further comprising one or more nucleotide sequences encoding one or more consensus influenza antigens selected from the group consisting of: consensus H1, consensus H3, and consensus H5. 
     
     
         68 . The composition of  claim 54 , wherein the composition comprises a DNA plasmid comprising the one or more nucleotide sequences. 
     
     
         69 . The composition of  claim 68 , wherein the DNA plasmid comprises a promoter operably linked to the one or more nucleotide sequences. 
     
     
         70 . The composition of  claim 54 , comprising a plurality of different DNA plasmids;
 Wherein one of the plurality of DNA plasmids comprises the nucleotide sequence that encodes the consensus NA,   one of the plurality of DNA plasmids comprises the nucleotide sequence that encodes the consensus M2e-NP, and   one of the plurality of DNA plasmids comprises a nucleotide sequence that encodes a consensus hemagglutinin (HA) antigen.   
     
     
         71 . A method of eliciting an immune response against influenza comprising administering to a subject a composition comprising one or more nucleotide sequences selected from the group consisting of:
 a) a nucleotide sequence encoding a consensus neuraminidase (NA) antigen, and   b) a nucleotide sequence encoding a consensus M2 ectodomain-nucleoprotein (M2e-NP) antigen.   
     
     
         72 . The method of  claim 71 , further comprising electroporating cells of the subject with a pulse of energy at a constant current effective to permit entry of the composition in the cells. 
     
     
         73 . The method of  claim 71 , wherein the administering step comprises injecting the composition intradermally, subcutaneously, or intramuscularly.