VACCINE AGAINST RSV

• US 20180200360A1
• Filed: 07/07/2016
• Published: 07/19/2018
• Est. Priority Date: 07/07/2015
• Status: Active Grant

• Current Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Original Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Inventors: LANGEDIJK, Johannes, ROYMANS, Dirk Andre Emmy
• Granted Patent: US 10,456,462 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/155 Paramyxoviridae, e.g. parainfluenza virus
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2760/18522 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/18534 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Compositions including a recombinant respiratory syncitial virus (RSV) Fusion (F) polypeptide that is stabilized in the pre-fusion conformation are described. The RSV F polypeptide includes at least one mutation as compared to a wild type RSV F polypeptide and the at least one mutation is a) a mutation of the amino acid aspartic acid (D) on position 486, b) a mutation of the amino acid aspartic acid (D) on position 489, or c) a mutation of the amino acid serine (S) on position 398 and/or the amino acid lysine (K) on position 394. Compositions including an isolated nucleic acid molecule encoding the stable RSV F polypeptides are also described.

Claims

1. A composition comprising a recombinant respiratory syncitial virus (RSV) Fusion (F) polypeptide that is stabilized in the pre-fusion conformation, wherein the RSV F polypeptide comprises at least one mutation as compared to a wild type RSV F polypeptide, wherein the at least one mutation is selected from the group consisting of:

a) a mutation of the amino acid aspartic acid (D) at position 486, b) a mutation of the amino acid aspartic acid (D) at position 489, and c) a mutation of the amino acid serine (S) at position 398 and/or the amino acid lysine (K) at position 394.

4. The composition according to claim 1, wherein the mutation of the amino acid at position 486 is a mutation from aspartic acid (D) to asparagine (N).

5. The composition according to claim 1, wherein the mutation of the amino acid at position 489 is a mutation from aspartic acid (D) to tyrosine (Y).

6. The composition according to claim 1, wherein the mutation of the amino acid at position 398 is a mutation from serine (S) to leucine (L) and/or the mutation at position 394 is a mutation of lysine (K) to arginine (R).

7. The composition according to claim 1, wherein the RSV F polypeptide is a full-length RSV protein.

8. The composition according to claim 1, wherein the RSV F polypeptide is a soluble RSV F protein.

9. The composition according to claim 1, wherein the polypeptide is stable for at least 10 minutes at 55°

C.

10. The composition according to claim 1, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

21-26.

11. A method of inducing an immune response against RSV F protein in a subject in need thereof, the method comprising administering to the subject the composition according to claim 1.

12. A vaccine comprising the composition according to claim 1.

13. A method of prophylaxis and/or treatment of RSV infection protein in a subject in need thereof, the method comprising administering to the subject the composition according to claim 1.

2. A composition comprising a nucleic acid sequence encoding a recombinant respiratory syncitial virus (RSV) Fusion (F) polypeptide that is stabilized in the pre-fusion conformation, wherein the RSV F polypeptide comprises at least one mutation as compared to a wild type RSV F polypeptide, wherein the at least one mutation is selected from the group consisting of:

a) a mutation of the amino acid aspartic acid (D) at position 486, b) a mutation of the amino acid aspartic acid (D) at position 489, and c) a mutation of the amino acid serine (S) at position 398 and/or the amino acid lysine (K) at position 394.

3. The composition according to claim 2, wherein the nucleic acid sequence is comprised in a vector.