Rotavirus mrna vaccine
AssigneeCureVac AG
InventorsSusanne RAUCH, Sandro ROIER, Benjamin PETSCH
Life of this patent
Estimating the term…
Abstract
The invention is directed to a coding RNA for a Rotavirus vaccine. The coding RNA comprises at least one coding region encoding at least one antigenic peptide or protein of a Rotavirus, in particular VPS* of a Rotavirus, or immunogenic fragment or immunogenic variant thereof. The present invention is also directed to compositions and vaccines comprising said coding RNA in association with a polymeric carrier, a polycationic protein or peptide, or a lipid nanoparticle (LNP). Further, the invention concerns a kit, particularly a kit of parts comprising the coding RNA, or the composition, or the vaccine. The invention is also directed to a kit or kit of parts, medical treatments, and the first and second medical uses.
Claims68
A coding RNA for a Rotavirus vaccine comprising
- a) at least one heterologous 5′ untranslated region (5′-UTR) and/or at least one heterologous 3′ untranslated region (3′-UTR);
- and
- b) at least one coding sequence operably linked to said 3′-UTR and/or 5′-UTR encoding at least one antigenic protein of a Rotavirus, wherein said antigenic protein is or is derived from VP8* or an immunogenic fragment or immunogenic variant thereof.
Coding RNA of any one of the preceding claims, wherein the Rotavirus is a Rotavirus A selected from the P-serotypes P[4], P[6] or P[8].
Coding RNA of any one of the preceding claims, wherein the Rotavirus is a Rotavirus A selected from Human rotavirus A BE1058 (RVA/Human-wt/BEL/BE1058/2008/G2P[4], G2P[4], JN849123.1, GI:371455744, AEX30665.1, acronym:
- RVA/BE1058/P[4]), Human rotavirus A F01322 (Hu/BEL/F01322/2009/G3P[6], G3P[6], JF460826.1, GI:
- 37531451, AFA51886.1, acronym:
- RVA/F01322/P[6]), Human rotavirus A BE1128 (RVA/Human-wt/BEL/BE1128/2009/G1P[8], G1P[8], JN849135.1. GI:
- 371455756, AEX30671, acronym:
- RVA/BE1128/P[8]), or Human rotavirus A WA-VirWa (Wa variant VirWa, G1P[8], ACR22783.1, GI:
- 237846292, FJ423116, acronym:
- RVA/Wa-VirWa/P[8]).
Coding RNA of any one of the preceding claims, wherein the VP8* is a full length VP8* protein having an amino acid sequence comprising or consisting of amino acid 1 to amino acid 240, or a fragment of a VP8* protein.
Coding RNA of any one of the preceding claims, wherein the amino acid sequences of the at least one antigenic protein derived from VP8* is mutated to delete at least one predicted or potential glycosylation site.
Coding RNA of any one of the preceding claims, wherein the amino acid sequences of the at least one antigenic protein derived from VP8* is mutated to delete all predicted or potential glycosylation sites.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence encodes at least one of the amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs:
- 19-45, or an immunogenic fragment or immunogenic variant of any of these.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence additionally encodes one or more heterologous peptide or protein elements selected from a signal peptide, a linker, a helper epitope, an antigen clustering domain, or a transmembrane domain.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence encodes the following elements preferably in N-terminal to C-terminal direction:
- a) helper epitope, VP8*protein or VP8*fragment;
- or
- b) helper epitope, VP8*protein or VP8*fragment;
- antigen clustering domain;
- or
- c) Signal peptide, helper epitope, VP8*protein or fragment thereof;
- or
- d) Signal peptide, helper epitope, VP8*protein or VP8*fragment, antigen clustering domain;
- or
- e) Signal peptide, helper epitope, VP8*protein or VP8*fragment, transmembrane domain;
- or
- f) antigen clustering domain, helper epitope;
- VP8*protein or VP8*fragment.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence encodes at least one of the amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs:
- 1-6, 46-117, 1899, 1900, or an immunogenic fragment or immunogenic variant of any of these.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence comprises a codon modified coding sequence comprising or consisting of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one SEQ ID NOs:
- 190-261, 298-369, 406-477, 514-585, 1901-1906, or a fragment or variant of any of these sequences.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence comprises at least one modified nucleotide selected from pseudouridine (LP) and N1-methylpseudouridine (ml P), preferably wherein all uracil nucleotides are replaced by pseudouridine (V) nucleotides and/or N1-methylpseudouridine (ml 4) nucleotides.
Coding RNA of any one of the preceding claims, wherein the at least one coding sequence is a codon modified coding sequence, wherein the amino acid sequence encoded by the at least one codon modified coding sequence is preferably not being modified compared to the amino acid sequence encoded by the corresponding wild type coding sequence.
Coding RNA of any one of the preceding claims, wherein the coding RNA is an mRNA, a self-replicating RNA, a circular RNA, a viral RNA, or a replicon RNA.
Coding RNA of any one of the preceding claims, wherein the coding RNA is an mRNA.
Coding RNA of any one of the preceding claims, wherein the coding RNA comprises a 5′-cap structure, preferably cap0, cap1, cap2, a modified cap0 or a modified cap1 structure.
Coding RNA of any one of the preceding claims, wherein the coding RNA comprises a cap1 structure, wherein said cap1 structure is obtainable by co-transcriptional capping preferably using a trinucleotide cap1 analogue.
Coding RNA of any one of the preceding claims, wherein the coding RNA comprises at least one poly(A) sequence comprising about 30 to about 200 adenosine nucleotides, preferably comprising about 100 adenosine nucleotides.
Coding RNA of any one of the preceding claims, wherein the RNA comprises at least one histone stem-loop, wherein the histone stem-loop preferably comprises or consists of a nucleic acid sequence identical or at least 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 1819 or 1820, or fragments or variants thereof.
Coding RNA of any one of the preceding claims, wherein the RNA comprises at least one 3′ terminal sequence element comprising or consisting of a nucleic acid sequence being identical or at least 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 1825-1856, or a fragment or variant thereof.
Coding RNA of any one of the preceding claims, wherein the at least one heterologous 3′-UTR comprises or consisting of a nucleic acid sequence derived from a 3′-UTR of a gene selected from PSMB3, ALB7, alpha-globin, CASP1, COX6B1, GNAS, NDUFA1 and RPS9, or from a homolog, a fragment or a variant of any one of these genes.
Coding RNA of any one of the preceding claims, wherein the at least one heterologous 5′-UTR comprises or consisting of a nucleic acid sequence derived from a 5′-UTR of a gene selected from HSD17B4, RPL32, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2, or from a homolog, a fragment or variant of any one of these genes.
Coding RNA of any one of the preceding claims, wherein
- the at least one heterologous 5′-UTR is derived from a 5′-UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and the at least one 3-UTR is derived from a 3′-UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, preferably wherein said 5′-UTR comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 1781 or 1782 or a fragment or a variant thereof, and wherein said 3′-UTR comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 1803 or 1804 or a fragment or a variant thereof;
- or
- the at least one heterologous 3′-UTR is derived from a 3′-UTR of a alpha-globin gene gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, preferably wherein said 3′-UTR comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 1817 or 1818 or a fragment or a variant thereof.
Coding RNA of any one of the preceding claims, wherein the coding RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 586-1737, 1862-1882, 1885-1898, 1907-1930 or a fragment or variant of any of these sequences.
Dependencies are inferred from the claim text.