Rabies vaccine
The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein of Rabies virus 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 Rabies virus 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 Rabies virus infections. The present invention further describes a method of treatment or prophylaxis of rabies using the mRNA sequence.
1. A method of stimulating a protective immune response to rabies virus in a subject comprising administering to the subject a pharmaceutical composition comprising a purified mRNA molecule, said mRNA comprising:
(a) a 5′ Cap;
(b) an open reading frame (ORF) encoding a Rabies virus glycoprotein (RAV-G), wherein the ORF comprises a sequence having at least about 95% identity to the protein coding region of SEQ ID NO: 24; and
(c) a Poly(A) sequence,
wherein the composition is administered by injection.
2. The method of claim 1 , wherein the composition is administered by intramuscular or intradermal injection.
3. The method of claim 2 , wherein the composition is administered by intramuscular injection.
4. The method of claim 1 , wherein the 5′ Cap is a m7GpppN Cap.
5. The method of claim 1 , wherein the mRNA comprises, from 5′ to 3′:
(a) a 5′ Cap;
(b) an open reading frame (ORF) encoding a Rabies virus glycoprotein (RAV-G); and
(c) a 3′ untranslated region (UTR), including the Poly(A) sequence.
6. The method of claim 5 , wherein the Poly(A) sequence comprises 50 to 250 adenosine nucleotides.
7. The method of claim 6 , wherein the mRNA further comprises a 5′ UTR sequence.
8. The method of claim 7 , wherein the 5′UTR is derived from the 5′-UTR of a TOP gene.
9. The method of claim 6 , wherein the 3′ UTR further comprises a histone stem-loop sequence.
10. The method of claim 6 , wherein the ORF has a G/C content that is increased compared with the G/C content an ORF from an original sequence encoding RAV-G.
11. The method of claim 6 , wherein the mRNA is formulated with a cationic or polycationic compound.
12. The method of claim 11 , wherein the a cationic or polycationic compound comprises a cationic lipid.
13. The method of claim 7 , wherein the mRNA comprises at least one base-modified nucleotide.
14. The method of claim 7 , wherein the poly(A) sequence is located at the 3′ terminus of the mRNA.
15. A method of stimulating a protective immune response to rabies virus in a subject comprising administering to the subject a pharmaceutical composition comprising a purified mRNA molecule, said mRNA comprising:
(a) a 5′ Cap;
(b) a 5′ untranslated region (UTR);
(c) an open reading frame (ORF) encoding a Rabies virus glycoprotein (RAV-G), wherein the ORF comprises a sequence having at least about 95% identity to the protein coding region of SEQ ID NO: 24;
(d) a 3′ UTR; and
(e) a Poly(A) sequence,
wherein the composition is administered by intramuscular injection and wherein the mRNA is formulated with cationic lipid.
16. The method of claim 15 , wherein the ORF has a G/C content that is increased compared with the G/C content an ORF from an original sequence encoding RAV-G or an antigenic fragment thereof.
17. The method of claim 15 , wherein the RAV-G is a full length RAV-G.
18. The method of claim 15 , wherein the mRNA comprises at least one base-modified nucleotide.