Respiratory syncytial virus (RSV) vaccine

Patent metadata

Field	Value
Publication number	US-9688729-B2
Application number	US-201615048439-A
Country	US
Kind code	B2
Filing date	Feb 19, 2016
Priority date	Aug 21, 2013
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein of RSV infections Respiratory syncytial virus (RSV) or a fragment, variant or derivative thereof. Additionally the present invention relates to a composition comprising a plurality of mRNA sequences comprising a coding region, encoding at least one antigenic peptide or protein of RSV infections Respiratory syncytial virus (RSV) or a fragment, variant or derivative thereof. Furthermore it also discloses the use of the mRNA sequence or the composition comprising a plurality of mRNA sequences for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the prophylaxis or treatment of RSV infections Respiratory syncytial virus (RSV) infections. The present invention further describes a method of treatment or prophylaxis of RSV infections using the mRNA sequence.

First claim

The invention claimed is:

1. A method of treatment or prophylaxis of Respiratory syncytial virus (RSV) infections comprising the steps:
a) Providing the mRNA sequence encoding at least one antigenic polypeptide from the fusion protein F, the nucleoprotein N, the M2-1 protein or the M2-2 protein of RSV, wherein the G/C content of the sequence encoding the antigenic polypeptide is increased compared with the G/C content of the coding region of the wild type mRNA encoding an antigenic polypeptide; and
b) applying or administering the mRNA sequence to a subject;
wherein the mRNA sequence encoding the antigenic polypeptide comprises a sequence at least 90% identical to one of Seq. Id. Nos. 31, 32, 33, 34, or 35.

2. The method according to claim 1 , wherein the mRNA further comprising a 5′-cap structure, a poly(A) sequence, and/or a poly(C) sequence.

3. The method according to claim 2 , wherein the 5′cap structure is m7GpppN.

4. The method according to claim 2 , wherein the poly(A) sequence comprises a sequence of 25 to 400 adenosine nucleotides.

5. The method according to claim 1 , wherein the mRNA further comprises at least one histone stem-loop.

6. The method according to claim 1 , wherein the mRNA sequence further comprises a stabilizing sequence from the alpha globin 3′ UTR, positioned 3′ relative to the coding region of the mRNA sequence.

7. The method according to claim 1 , wherein the mRNA sequence comprises from a 5′ to 3′: a 5′-cap structure, a 5′ UTR sequence, the sequence encoding the at least one antigenic polypeptide, a 3′ UTR, a poly(A) sequence, a poly(C) sequence and a histone stem-loop sequence.

8. The method according to claim 1 , wherein the at least one antigenic polypeptide is from the RSV fusion protein F.

9. The method according to claim 1 , wherein the mRNA sequence is complexed with a cationic or polycationic compound.

10. The method according to claim 9 , wherein the cationic or polycationic compound is protamine, poly-L-lysine (PLL), or poly-arginine.

11. The method according to claim 9 , wherein the cationic or polycationic compound is protamine.

12. The method according to claim 9 , wherein the weight ratio of the mRNA sequence to the cationic or polycationic compound is in the range from 6:1 to 0.25:1.

13. The method of claim 1 , wherein the mRNA sequence is administered by injection.

14. The method of claim 13 , wherein the mRNA sequence is administered by intradermal or intramuscular injection.

15. The method of claim 1 , wherein the mRNA sequence is formulated in a Ringer's lactate solution.

16. The method of claim 1 , further comprising administering mRNA sequences encoding at least 2 different antigenic polypeptides from RSV.

17. The method of claim 16 , wherein the mRNA sequences encoding the at least 2 different antigenic polypeptides are administered separately.

18. The method of claim 16 , wherein the mRNA sequences encoding the at least 2 different antigenic polypeptides are administered in the same formulation.

19. The method according to claim 1 , wherein the mRNA sequence encoding the antigenic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 31, 32, 33, 34 or 35.

20. The method according to claim 19 , wherein the mRNA sequence encoding the antigenic polypeptide comprises a sequence according to SEQ ID NO: 31, 32, 33, 34 or 35.

21. The method of claim 1 , further defined as method for inducing RSV-specific T-cell response in the subject.

Assignees

• Curevac Ag

Inventors

• Kramps Thomas
• Schnee Margit
• Voss Daniel
• Petsch Benjamin

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K2039/6031

  Proteins · CPC title