Enhanced influenza hemagglutinin binders

1. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein the polypeptide does not comprise the amino acid sequence of 1u84 (SEQ ID NO: 5).

2. The isolated polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO:2.

3. The isolated polypeptide of claim 1 , wherein residue 46 is selected from the group consisting of R, Y, C, and W.

4. The isolated polypeptide of claim 1 , wherein residue 46 is R.

5. The isolated polypeptide of claim 1 , wherein residue 46 is R and one or more of the following is true:

(a) residue 16 is N;

(b) residue 31 is T;

(c) residue 33 is Q;

(d) residue 70 is R; and

(e) residue 71 is T.

6. The isolated polypeptide of claim 1 , wherein one or more of the following is true:

(a) residue 45 is N;

(b) residue 65 is R; and

(c) residue 66 is L.

7. The isolated polypeptide of claim 1 , comprising a polypeptide at least 90% identical to the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:4.

8. The isolated polypeptide of claim 1 , wherein one or more of the following are true:

(a) residue 33 is A, C, T, or S;

(b) residue 46 is H;

(c) residue 59 is F, W, or Y; and

(d) residue 63 is P.

9. The isolated polypeptide of claim 1 , wherein one or more of the following are true:

(a) residue 33 is C, S, A, T, or V;

(b) residue 53 is a small smaller polar/charged residue;

(c) residue 55 is S, T, or A;

(d) residue 59 is L, P, or Y;

(e) residue 68 is L;

(f) residue 72 is W; and

(g) residue 73 is E.

10. The isolated polypeptide of claim 1 , wherein one or more of the following are true:

(a) residue 36 is K;

(b) residue 52 is L;

(c) residue 53 is a small polar or charged AA; and

(d) residue 59 is Y or F.

11. The isolated polypeptide of claim 1 , wherein one or more of the following are true:

(a) residue 33 is P;

(b) residue 69 is Y;

(c) residue 70 is a polar or charged AA; and

(d) residue 73 is E.

12. The isolated polypeptide of claim 1 , wherein one or more of the following are true:

(a) residue 31 is any amino acid other than a charged amino acid;

(b) residue 33 is S or T;

(c) residue 52 is L;

(d) residue 53 is a small polar or charged AA and is not R;

(e) residue 59 is V;

(f) residue 69 is a negative AA;

(g) residue 70 is any non-positively charged AA;

(h) residue 72 is a negative AA;

(i) residue 73 is a negative AA; and

(j) residue 76 is any amino acid other than R, such as a negative AA.

13. The isolated polypeptide of claim 1 , wherein one or more of the following are true:

(a) residue 46 is H;

(b) residue 53 is a small polar or charged AA;

(c) residue 63 is R; and

(d) residue 76 is a negative AA.

14. The isolated polypeptide of claim 8 , wherein all of the listed residue options are true.

15. The isolated polypeptide according to claim 1 , wherein the polypeptide comprises a tag.

16. An isolated nucleic acid encoding the polypeptide of claim 1 .

17. A recombinant expression vector comprising the nucleic acid of claim 16 , operatively linked to a suitable control sequence.

18. A recombinant host cell comprising the recombinant expression vector of claim 17 .

19. A pharmaceutical composition, comprising one or more polypeptides according to claim 1 and a pharmaceutically acceptable carrier.

20. A method for treating and/or limiting an influenza infection, comprising administering to a subject in need thereof a therapeutically effective amount of one or more polypeptides of claim 1 , salts thereof, conjugates thereof, or pharmaceutical compositions thereof, to treat and/or limit the influenza infection.

21. The method of claim 20 , wherein the therapeutically effective amount of one or more polypeptides, salts thereof, conjugates thereof, or pharmaceutical compositions thereof are administered mucosally.

22. The method of claim 21 , wherein the mucosal administration comprises intranasal administration.

23. The method of claim 20 , wherein the therapeutically effective amount of one or more polypeptides, salts thereof, conjugates thereof, or pharmaceutical compositions thereof are administered orally.

24. The method of claim 20 , wherein the subject is immune-compromised and/or is 65 years of age or older.

25. A method for diagnosing an influenza infection, or monitoring progression of an influenza infection, comprising

(a) contacting a biological sample from a subject suspected of having an influenza infection with a diagnostically effective amount of one or more polypeptides of claim 1 , under conditions suitable for binding of the polypeptide to a viral HA protein present in the sample; and

(b) detecting polypeptide-viral HA binding complexes,

where the presence of such binding complexes indicates that the subject has an influenza infection, or provides a measure progression of an influenza infection.

26. A method for identifying candidate influenza vaccines, comprising

contacting test compounds with one or more polypeptides of claim 1 under conditions suitable for polypeptide binding;

removing unbound test compounds; and

identifying those test compounds that bind to the polypeptide of the invention, wherein such test compounds are candidate influenza vaccines.

27. A method for identifying candidate compounds for treating, limiting, and/or diagnosing influenza infection, comprising

contacting an influenza HA protein with (i) test compounds and (ii) a polypeptide of claim 1 , under conditions suitable for binding of the HA protein to the polypeptide of the present invention; and

identifying those test compounds that outcompete the polypeptide for binding to the HA protein, wherein such test compounds are candidate compounds for treating, limiting, and/or diagnosing influenza infection.