Computationally optimized broadly reactive antigens for H1N1 influenza

Patent metadata

Field	Value
Publication number	US-9580475-B2
Application number	US-201214126550-A
Country	US
Kind code	B2
Filing date	Jun 20, 2012
Priority date	Jun 20, 2011
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

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. A recombinant influenza hemagglutinin (HA) polypeptide comprising:
(i) an amino acid sequence at least 99% identical to SEQ ID NO: 1, wherein the amino acid sequence of the polypeptide comprises no more than 5 amino acid substitutions relative to SEQ ID NO: 1;
(ii) the amino acid sequence of SEQ ID NO: 2;
(iii) an amino acid sequence at least 99% identical to SEQ ID NO: 3, wherein the amino acid sequence of the polypeptide comprises no more than 6 amino acid substitutions relative to SEQ ID NO: 3;
(iv) an amino acid sequence at least 99% identical to SEQ ID NO: 4, wherein the amino acid sequence of the polypeptide comprises no more than 8 amino acid substitutions relative to SEQ ID NO: 4;
(v) an amino acid sequence at least 98% identical to SEQ ID NO: 5, wherein the amino acid sequence of the polypeptide comprises no more than 10 amino acid substitutions relative to SEQ ID NO: 5;
(vi) an amino acid sequence at least 99% identical to SEQ ID NO: 6, wherein the amino acid sequence of the polypeptide comprises no more than 8 amino acid substitutions relative to SEQ ID NO: 6;
(vii) an amino acid sequence at least 97% identical to SEQ ID NO: 7, wherein the amino acid sequence of the polypeptide comprises no more than 10 amino acid substitutions relative to SEQ ID NO: 7;
(viii) an amino acid sequence at least 99% identical to SEQ ID NO: 8, wherein the amino acid sequence of the polypeptide comprises no more than 10 amino acid substitutions relative to SEQ ID NO: 8;
(ix) the amino acid sequence of SEQ ID NO: 9;
(x) an amino acid sequence at least 99% identical to SEQ ID NO: 10, wherein the amino acid sequence of the polypeptide comprises no more than 8 amino acid substitutions relative to SEQ ID NO: 10; or
(xi) an amino acid sequence at least 99% identical to SEQ ID NO: 11, wherein the amino acid sequence of the polypeptide comprises no more than 5 amino acid substitutions relative to SEQ ID NO: 11.

2. The influenza HA polypeptide of claim 1 , comprising the amino acid sequence 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.

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

4. A method of eliciting an immune response to influenza virus in a subject, comprising administering the composition of claim 3 to the subject.

5. The method of claim 4 , wherein the composition further comprises an adjuvant.

6. The method of claim 4 , wherein the composition is administered intramuscularly.

Assignees

• Ross Ted M
• Crevar Corey J
• 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

• A61K2039/55505

  Inorganic adjuvants · CPC title

• A61K2039/5258

  Virus-like particles · CPC title

• A61K39/145 Primary

  Orthomyxoviridae, e.g. influenza virus · CPC title