Influenza nucleic acid molecules and vaccines made therefrom
Provided herein are nucleic acid sequences that encode novel consensus amino acid sequences of HA 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 using the vaccines that are provided.
1. An isolated nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
i) a nucleic acid sequence selected from the group consisting of: SEQ ID NO:1, a nucleic acid sequence that is 95% identical to SEQ ID NO:1; a fragment of SEQ ID NO:1 comprising at least 240 nucleotides, and a nucleic acid sequence that is 99% identical to a fragment of SEQ ID NO:1 comprising at least 240 nucleotides;
ii) a nucleic acid sequence is selected from the group consisting of: SEQ ID NO:3, a nucleic acid sequence that is 95% identical to SEQ ID NO:3; a fragment of SEQ ID NO:3 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:3 comprising at least 60 nucleotides;
iii) a nucleic acid sequence selected from the group consisting of: SEQ ID NO:6, a nucleic acid sequence that is 95% identical to SEQ ID NO:6; a fragment of SEQ ID NO:6 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:6 comprising at least 60 nucleotides;
iv) a nucleic acid sequence selected from the group consisting of: SEQ ID NO:9, a nucleic acid sequence that is 95% identical to SEQ ID NO:9; a fragment of SEQ ID NO:9 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:9 comprising at least 60 nucleotides;
v) a nucleic acid sequence selected from the group consisting of: SEQ ID NO:11, a nucleic acid sequence that is 95% identical to SEQ ID NO:11; a fragment of SEQ ID NO:11 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:11 comprising at least 60 nucleotides.
2. The isolated nucleic acid molecule of claim 1 comprising a nucleic acid sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, and SEQ ID NO:11.
3. The isolated nucleic acid molecule of claim 1 comprising a nucleic acid sequence selected from the group consisting of: a nucleic acid sequence that is 95% identical to SEQ ID NO:1, a nucleic acid sequence that is 95% identical to SEQ ID NO:3, a nucleic acid sequence that is 95% identical to SEQ ID NO:6, a nucleic acid sequence that is 95% identical to SEQ ID NO:9, and a nucleic acid sequence that is 95% identical to SEQ ID NO:11.
4. The isolated nucleic acid molecule of claim 1 comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:6, and SEQ ID NO:9.
5. An expression vector comprising a nucleic acid sequence of claim 1 operably linked to regulatory elements.
6. The expression vector of claim 5 wherein said expression vector is a plasmid.
7. A composition comprising a) a plurality of one or more nucleic acid molecules comprising one or more nucleic acid sequences selected from the group consisting of:
i) a nucleic acid selected from the group consisting of: SEQ ID NO:1, a nucleic acid sequence that is 95% identical to SEQ ID NO:1; a fragment of SEQ ID NO:1 comprising at least 240 nucleotides, and a nucleic acid sequence that is 99% identical to a fragment of SEQ ID NO: 1 comprising at least 240 nucleotides;
ii) a nucleic acid sequence is selected from the group consisting of: SEQ ID NO:3, a nucleic acid sequence that is 95% identical to SEQ ID NO:3; a fragment of SEQ ID NO:3 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:3 comprising at least 60 nucleotides;
iii) a nucleic acid sequence is selected from the group consisting of: SEQ ID NO:6, a nucleic acid sequence that is 95% identical to SEQ ID NO:6; a fragment of SEQ ID NO:6 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:6 comprising at least 60 nucleotides;
iv) a nucleic acid sequence is selected from the group consisting of: SEQ ID NO:9, a nucleic acid sequence that is 95% identical to SEQ ID NO:9; a fragment of SEQ ID NO:9 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:9 comprising at least 60 nucleotides;
v) a nucleic acid sequence is selected from the group consisting of: SEQ ID NO:11, a nucleic acid sequence that is 95% identical to SEQ ID NO:11; a fragment of SEQ ID NO:11 comprising at least 60 nucleotides, and a nucleic acid sequence that is 95% identical to a fragment of SEQ ID NO:11 comprising at least 60 nucleotides; and
b) one or more additional nucleic acid sequences that encode one or more proteins selected from the group consisting of one or more of: an influenza A hemagglutinin H1, an influenza A hemagglutinin H2, an influenza A hemagglutinin H3, influenza A hemagglutinin H4, influenza A hemagglutinin H5, influenza A hemagglutinin H6, an influenza A hemagglutinin H7, an influenza A hemagglutinin H8, an influenza A hemagglutinin H9, an influenza A hemagglutinin H10, an influenza A hemagglutinin H11, an influenza A hemagglutinin H12, influenza A hemagglutinin H13, influenza A hemagglutinin H14, an influenza A hemagglutinin H15, influenza A hemagglutinin H16, an influenza A neuraminidase N1, an influenza A neuraminidase N2, an influenza A neuraminidase N3, an influenza A neuraminidase N4, an influenza A neuraminidase N5, an influenza A neuraminidase N6, an influenza A neuraminidase N7, an influenza A neuraminidase N8, an influenza A neuraminidase N9, an influenza B hemagglutinin and an influenza B neuraminidase.
8. The composition of claim 7 wherein said one or more additional nucleic acid sequences are on a plurality of one or more different nucleic acid molecules from the plurality of nucleic acid molecules set forth in section a).
9. The composition of claim 7 wherein the plurality of nucleic acid molecules set forth in section a) comprises one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, and SEQ ID NO:11.
10. The composition of claim 7 wherein the plurality of nucleic acid molecules set forth in section a) comprises one or more nucleic acid sequences selected from the group consisting of: a nucleic acid sequence that is 95% identical to SEQ ID NO:1, a nucleic acid sequence that is 95% identical to SEQ ID NO:3, a nucleic acid sequence that is 95% identical to SEQ ID NO:6, a nucleic acid sequence that is 95% identical to SEQ ID NO:9, and a nucleic acid sequence that is 95% identical to SEQ ID NO:11.
11. The composition of claim 7 wherein the nucleic acid sequences set forth in a) and b) are each operably linked to regulatory elements.
12. The composition of claim 7 wherein the nucleic acid sequences set forth in a) and b) are each operably linked to regulatory elements that are functional in a human cell.
13. The composition of claim 7 wherein the nucleic acid sequences set forth in a) and b) are part of one or more expression vectors.
14. The composition of claim 7 wherein the one or more expression vectors are plasmids.
15. The composition of claim 7 comprising pGX2009 and/or pGX2006.
16. The composition of claim 7
comprising one or more of:
a nucleic acid sequence comprising SEQ ID NO:1;
a nucleic acid sequence comprising SEQ ID NO:6;
a nucleic acid sequence comprising SEQ ID NO:9;
a nucleic acid sequence comprising SEQ ID NO:13;
a nucleic acid sequence that encodes an influenza A hemagglutinin H1;
and a nucleic acid sequence that encodes an influenza A hemagglutinin H3.
17. The composition of claim 7 , wherein the one or more additional nucleic acids encode an influenza A hemagglutinin H1 comprising SEQ ID NO:19 and an influenza A hemagglutinin H3 comprising SEQ ID NO:20.
18. The composition of claim 16 comprising:
a nucleic acid molecule comprising SEQ ID NO:9;
a nucleic acid molecule comprising SEQ ID NO:13; and
a nucleic acid molecule that encodes an influenza A hemagglutinin H3 comprising SEQ ID NO:20.
19. The composition of claim 18 wherein
the nucleic acid molecule comprising SEQ ID NO:9 is a plasmid;
the nucleic acid molecule comprising SEQ ID NO:13 is a plasmid; and
the nucleic acid molecule that encodes an influenza A hemagglutinin H3 comprising SEQ ID NO:20 is a plasmid.