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 method of stimulating an immune response to Respiratory syncytial virus (RSV) in a subject comprising administering to the subject a pharmaceutical composition comprising an mRNA molecule having a coding sequence encoding a fusion (F) protein of RSV with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence being 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 complexed with a cationic or polycationic compound.
2. The method of claim 1 , wherein the mRNA further comprises a poly(C) sequence.
3. The method of claim 1 , wherein the 5′-cap structure is m7GpppN.
4. The method of claim 1 , wherein the poly(A) sequence comprises a sequence of 25 to 400 adenosine nucleotides.
5. The method of claim 1 , wherein the mRNA further comprises at least one histone stem-loop.
6. The method of claim 1 , wherein the mRNA sequence comprises a stabilizing sequence from the alpha globin 3′ UTR, positioned 3′ relative to the coding sequence of the mRNA sequence.
7. The method of claim 3 , wherein the poly(A) sequence comprises 60 to 250 adenosine nucleotides.
8. The method of claim 1 , wherein the mRNA further comprises at least one histone stem-loop.
9. The method of claim 7 , wherein the cationic or polycationic compound comprises a cationic lipid.
10. The method of claim 1 , wherein the composition comprises at least a second different mRNA encoding the second antigenic polypeptide from RSV.
11. The method of claim 1 , wherein the at least second different mRNA encodes an antigen from a different virus or an antigenic fragment thereof.
12. The method of claim 7 , wherein the 5′-cap structure is a Cap1 structure.
13. The method of claim 1 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.
14. The method of claim 1 , wherein the pharmaceutical composition is administered by intradermal or intramuscular injection.
15. The method of claim 14 , wherein the pharmaceutical composition is administered by intramuscular injection.