Respiratory syncytial virus (RSV) vaccine
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.
1. A pharmaceutical composition comprising a mRNA molecule having a coding sequence encoding a Respiratory Syncytial Virus fusion protein (RSV-F) with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence comprising a nucleic acid sequence at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33, wherein the mRNA comprises from 5′ to 3′: (i) a 5′-cap structure, (ii) a 5′ untranslated region (UTR); (iii) the coding sequence encoding the F protein; (iv) a 3′ UTR and (v) a poly(A) sequence, wherein the mRNA molecule is formulated with a cationic lipid.
2. The pharmaceutical composition of claim 1 , wherein the 5′ structure is m7GpppN.
3. The pharmaceutical composition of claim 1 , wherein the 5′ cap structure is a Cap1 structure.
4. The pharmaceutical composition of claim 1 , wherein the poly(A) sequence comprises a sequence of 25 to 400 adenosine nucleotides.
5. The pharmaceutical composition of claim 4 , wherein the poly(A) sequence comprises 60 to 250 adenosine nucleotides.
6. The pharmaceutical composition of claim 5 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.
7. The pharmaceutical composition of claim 1 , wherein the 3′ UTR comprises a stabilizing sequence from the alpha globin 3′ UTR.
8. The pharmaceutical composition of claim 1 , wherein the composition comprises at least a second, different, mRNA encoding an antigen from a different virus or an antigenic fragment thereof.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for intramuscular injection.
10. The pharmaceutical composition of claim 1 , wherein the encoded RSV-F comprises the transmembrane domain of native RSV-F.
11. The pharmaceutical composition of claim 10 , wherein the poly(A) sequence comprises 60 to 250 adenosine nucleotides.
12. The pharmaceutical composition of claim 11 , wherein the 5′ cap structure is a Cap1 structure.
13. A method of stimulating an immune response to Respiratory Syncytial Virus (RSV) in a subject comprising administering to the subject a pharmaceutical composition comprising a mRNA molecule having a coding sequence encoding a RSV fusion protein (RSV-F) with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence comprising a nucleic acid sequence at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33, wherein the mRNA comprises from 5′ to 3′: (i) a 5′-cap structure, (ii) a 5′ untranslated region (UTR); (iii) the coding sequence encoding the F protein; (iv) a 3′ UTR and (v) a poly(A) sequence of 60 to 250 adenosine nucleotides, wherein the mRNA molecule is formulated with a cationic lipid.
14. The method of claim 13 , wherein the pharmaceutical composition is administered by intramuscular injection.
15. The method of claim 14 , wherein the 5′ cap structure is m7GpppN.
16. The method of claim 14 , wherein the 5′ structure is a Cap1 structure.
17. The method of claim 14 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.
18. The method of claim 14 , wherein the 3′ UTR comprises a stabilizing sequence from the alpha globin 3′ UTR.
19. The method of claim 14 , wherein the composition comprises at least a second, different, mRNA encoding an antigen from a different virus or an antigenic fragment thereof.
20. The method of claim 14 , wherein the encoded RSV-F comprises the transmembrane domain of native RSV-F.
21. A method of stimulating an immune response to Respiratory Syncytial Virus (RSV) in a subject comprising administering to the subject a pharmaceutical composition comprising a mRNA molecule having a coding sequence encoding a RSV fusion protein (RSV-F) with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence comprising a nucleic acid sequence at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33, wherein the mRNA comprises from 5′ to 3′: (i) a 5′ cap structure, (ii) a 5′ untranslated region (UTR); (iii) the coding sequence encoding the F protein; (iv) a 3′ UTR and (v) a poly(A) sequence of 60 to 250 adenosine nucleotides, wherein the mRNA molecule is formulated with a cationic component and wherein the immune response stimulated by the pharmaceutical composition produces an increased amount of RSV neutralizing antibodies compared to a composition comprising a mRNA encoding a full length RSV-F.
22. The method of claim 21 , wherein the pharmaceutical composition is administered by intradermal or intramuscular injection.
23. The method of claim 22 , wherein the pharmaceutical composition is administered by intramuscular injection.
24. The method of claim 22 , wherein the mRNA molecule is formulated with a cationic lipid.
25. The method of claim 22 , wherein the 5′ cap structure is m7GpppN.
26. The method of claim 22 , wherein the 5′ structure is a Cap1 structure.
27. The method of claim 22 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.
28. The method of claim 22 , wherein the 3′ UTR comprises a stabilizing sequence from the alpha globin 3′ UTR.
29. The method of claim 22 , wherein the composition comprises at least a second, different, mRNA encoding an antigen from a different virus or an antigenic fragment thereof.
30. The method of claim 22 , wherein the encoded RSV-F comprises the transmembrane domain of native RSV-F.