Computationally optimized broadly reactive antigens for h1n1 influenza

Patent metadata

Field	Value
Publication number	US-2018371025-A1
Application number	US-201816119501-A
Country	US
Kind code	A1
Filing date	Aug 31, 2018
Priority date	Jun 20, 2011
Publication date	Dec 27, 2018
Grant date	—

Abstract

Described herein is the generation of optimized HIN1 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

1 . An influenza virus-like particle (VLP) comprising an influenza hemagglutinin (HA) polypeptide, wherein the amino acid sequence of the HA 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; (x) no more than 8 amino acid substitutions relative to SEQ ID NO: 10; or (xi) no more than 5 amino acid substitutions relative to SEQ ID NO: 11.

2 . The influenza VLP of claim 1 , wherein the influenza HA 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.

3 . The influenza VLP of claim 1 , further comprising an influenza neuraminidase (NA) protein, an influenza matrix (M1) protein, or both.

4 . A composition comprising the VLP of claim 1 , and a pharmaceutically acceptable carrier.

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

6 . A method of immunizing a subject against influenza virus, comprising administering the VLP of claim 1 to the subject.

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

8 . A method of immunizing a subject against influenza virus, comprising administering the composition of claim 4 to the subject.

9 . The method of claim 8 , wherein the composition further comprises an adjuvant.

10 . The method of claim 8 , wherein the composition is administered intramuscularly.

11 . The method of claim 8 , wherein the composition comprises about 1 to about 25 μg of the VLP.

12 . The method of claim 8 , wherein the composition comprises about 15 μg of the VLP.

13 . A fusion protein comprising an influenza hemagglutinin (HA) polypeptide and a heterologous protein, wherein the amino acid sequence of the HA 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; (x) no more than 8 amino acid substitutions relative to SEQ ID NO: 10; or (xi) no more than 5 amino acid substitutions relative to SEQ ID NO: 11.

14 . A composition comprising the fusion protein of claim 13 , and a pharmaceutically acceptable carrier.

15 . A method of eliciting an immune response to influenza virus in a subject, comprising administering the fusion protein of claim 13 to the subject.

16 . A method of eliciting an immune response to influenza virus in a subject, comprising administering the composition of claim 14 to the subject.

17 . The method of claim 16 , wherein the composition further comprises an adjuvant.

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

Assignees

• Univ Pittsburgh Commonwealth Sys Higher Education

Inventors

• Ross Ted M
• Crevar Corey J

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61K39/12 Primary

  Viral antigens · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title

• C12N2760/16123

  Virus like particles [VLP] · CPC title