Computationally optimized broadly reactive antigens for H1N1 influenza

Patent metadata

Field	Value
Publication number	US-10093703-B2
Application number	US-201715407502-A
Country	US
Kind code	B2
Filing date	Jan 17, 2017
Priority date	Jun 20, 2011
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

Described herein is the generation of optimized H1N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H1N1 influenza virus isolates. 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 1918-2011. Provided herein are optimized H1N1 HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.

First claim

The invention claimed is:

1. An isolated nucleic acid molecule encoding a recombinant influenza hemagglutinin (HA) polypeptide, wherein the amino acid sequence of the polypeptide comprises:
(i) no more than 5 amino acid substitutions relative to SEQ ID NO: 1;
(ii) SEQ ID NO: 2;
(iii) no more than 6 amino acid substitutions relative to SEQ ID NO: 3;
(iv) no more than 8 amino acid substitutions relative to SEQ ID NO: 4;
(v) no more than 10 amino acid substitutions relative to SEQ ID NO: 5;
(vi) no more than 8 amino acid substitutions relative to SEQ ID NO: 6;
(vii) no more than 10 amino acid substitutions relative to SEQ ID NO: 7;
(viii) no more than 10 amino acid substitutions relative to SEQ ID NO: 8;
(ix) SEQ ID NO: 9;
(ix) no more than 8 amino acid substitutions relative to SEQ ID NO: 10; or
(x) no more than 5 amino acid substitutions relative to SEQ ID NO: 11.

2. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is codon-optimized for expression in mammalian cells.

3. A vector comprising the nucleic acid molecule of claim 1 .

4. The vector of claim 3 , further comprising a promoter operably linked to the nucleic acid sequence encoding the influenza HA polypeptide.

5. An isolated cell comprising the vector of claim 3 .

6. The isolated nucleic acid molecule of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10 or SEQ ID NO: 11.

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

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

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

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

11. The isolated nucleic acid molecule of claim 1 , wherein the amino acid sequence of the polypeptide consists of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11.

12. The isolated nucleic acid molecule of claim 11 , wherein the nucleic acid molecule is codon-optimized for expression in mammalian cells.

13. A vector comprising the nucleic acid molecule of claim 11 .

14. The vector of claim 13 , further comprising a promoter operably linked to the nucleic acid sequence encoding the influenza HA polypeptide.

15. An isolated cell comprising the vector of claim 13 .

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Ross Ted M
• Crevar Corey J

Classifications

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C12N2760/16122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N2760/16134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• A61K2039/5258

  Virus-like particles · CPC title