Computationally optimized broadly reactive antigens for H1N1 influenza

Patent metadata

Field	Value
Publication number	US-9309290-B2
Application number	US-201314092371-A
Country	US
Kind code	B2
Filing date	Nov 27, 2013
Priority date	Nov 27, 2012
Publication date	Apr 12, 2016
Grant date	Apr 12, 2016

Abstract

The generation of optimized H1N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H1N1 influenza virus isolates is described. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on selected H1N1 viruses isolated from 1918-2012. Optimized H1N1 HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides are described. Condon-optimized nucleic acid sequences encoding the HA polypeptides are also described. Methods of eliciting an immune response against influenza virus in a subject are also described.

First claim

The invention claimed is:

1. A recombinant influenza hemagglutinin (HA) polypeptide, comprising:
(i) the amino acid sequence of SEQ ID NO: 1 or the amino acid sequence of residues 2-566 of SEQ ID NO: 1;
(ii) the amino acid sequence of SEQ ID NO: 2 with no more than 2 amino acid substitutions relative to SEQ ID NO: 2 or the amino acid sequence of residues 2-566 of SEQ ID NO: 2;
(iii) the amino acid sequence of SEQ ID NO: 3 or the amino acid sequence of residues 2-566 of SEQ ID NO: 3;
(iv) the amino acid sequence of SEQ ID NO: 5 or the amino acid sequence of residues 2-566 of SEQ ID NO: 5;
(v) the amino acid sequence of SEQ ID NO: 6 with no more than 4 amino acid substitutions relative to SEQ ID NO: 6 or the amino acid sequence of residues 2-565 of SEQ ID NO: 6; or
(vi) the amino acid sequence of SEQ ID NO: 7 or the amino acid sequence of residues 2-566 of SEQ ID NO: 7.

2. The recombinant influenza HA polypeptide of claim 1 , comprising no more than 1 amino acid substitution relative to SEQ ID NO: 2 or no more than 3 amino acid substitutions relative to SEQ ID NO: 6.

3. The recombinant influenza HA polypeptide of claim 1 , comprising the amino acid sequence of residues 2-566 of SEQ ID NO: 2 or residues 2-565 of SEQ ID NO 6.

4. The recombinant influenza HA polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 6.

5. The recombinant influenza HA polypeptide of claim 1 , consisting of the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7.

6. An isolated nucleic acid encoding the influenza HA polypeptide of claim 1 .

7. The isolated nucleic acid of claim 6 , wherein the nucleic acid is codon-optimized for expression in mammalian cells.

8. A vector comprising the nucleic acid of claim 6 .

9. The vector of claim 8 , further comprising a promoter operably linked to the nucleic acid encoding the influenza HA polypeptide.

10. An isolated cell comprising the vector of claim 8 .

11. A fusion protein comprising the influenza HA polypeptide of claim 1 .

12. A composition comprising the influenza HA polypeptide of claim 1 and a pharmaceutically acceptable carrier.

13. A method of eliciting an immune response to influenza virus in a subject, comprising administering to the subject the influenza HA polypeptide of claim 1 .

14. A method of eliciting an immune response to influenza virus in a subject, comprising administering to the subject a composition comprising the influenza HA polypeptide of claim 1 and pharmaceutically acceptable carrier.

15. The method of claim 14 , wherein the composition further comprises an adjuvant.

16. The method of claim 14 , wherein the composition is administered intramuscularly.

Assignees

• Univ Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Ross Ted M
• Crevar Corey J
• Carter Jr Donald M

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C12N9/2402

  hydrolysing O- and S- glycosyl compounds (3.2.1) · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• C07K14/005 Primary

  from viruses · CPC title