Nucleic acid molecules and uses thereof

A method of stimulating an anti-Norovirus immune response in a mammalian subject comprising administering to the subject a pharmaceutical composition comprising at least three different artificial mRNA molecules, said at least three different artificial mRNA molecules comprising at least three different coding regions each encoding a different Norovirus VP1 polypeptide,

• wherein the artificial mRNA molecules each comprise, from 5′ to 3′:
• (i) a 5′ Cap structure;
• (ii) a heterologous 5′ untranslated region (UTR);
• (iii) the coding region encoding the Norovirus VP1 polypeptide;
• (iv) a heterologous 3′ UTR;
• and (v) a poly(A) sequence of 10 to 200 consecutive adenosine nucleotides,
• wherein the at least three different coding regions encode at least one GII.4 VP1 polypeptide and at least one GI VP1 polypeptide, wherein said GII.4 VP1 polypeptide is at least 95% identical to the polypeptide sequence of SEQ ID NO:
• 624 and wherein said GII.4 VP1 polypeptide is encoded by a RNA sequence at least 85% identical to the RNA sequence of SEQ ID NO:
• 22674,
• wherein said artificial mRNA molecules are complexed with a cationic or polycationic compound,
• wherein the composition is administered by intramuscular or intradermal injection, and
• wherein the method stimulates production of anti-Norovirus antibodies in the subject to each of the Norovirus VP1 polypeptides encoded by the artificial mRNA molecules.

A pharmaceutical composition comprising at least three different artificial mRNA molecules, said at least three different artificial mRNA molecules comprising at least three different coding regions each encoding a different Norovirus VP1 polypeptide,

• wherein the artificial mRNA molecules each comprise, from 5′ to 3′:
• (i) a 5′ Cap structure;
• (ii) a heterologous 5′ untranslated region (UTR);
• (iii) a coding region encoding a Norovirus VP1 polypeptide;
• (iv) a heterologous 3′ UTR;
• and (v) a poly(A) sequence of 10 to 200 consecutive adenosine nucleotides,
• wherein the at least three different artificial mRNA molecules each encode a different Norovirus VP1 polypeptide, wherein the at least three different artificial mRNA molecules encode at least one GII.4 VP1 polypeptide and at least one GI VP1 polypeptide, wherein said GII.4 VP1 polypeptide is at least 95% identical to the polypeptide sequence of SEQ ID NO:
• 624 and wherein said GII.4 VP1 polypeptide is encoded by a RNA sequence at least 85% identical to the RNA sequence of SEQ ID NO:
• 22674,
• wherein the artificial mRNA molecules optionally comprise a modified nucleobase moiety selected from the group consisting of pseudouridine and 1-methyl-pseudouridine,
• wherein said artificial mRNA molecules are complexed with a cationic or polycationic compound.