Trimeric S1-CD40L fusion protein vaccine against Middle East respiratory syndrome-coronavirus
An immunogenic CD40-targeted trimeric MERS-CoV S1 fusion polypeptide as well as a corresponding polynucleotide encoding it and its use for safely inducing immune responses directed against MERS-CoV without inducing vaccine associated respiratory pathologies associated with non-targeted vaccines.
1. A polypeptide that comprises at least one receptor-binding domain, immunogenic fragment, or epitope of S1 polypeptide of Middle East respiratory syndrome coronavirus (MERS-CoV), at least one trimerization motif, and at least one ligand for CD40;
wherein the at least one trimerization motif comprises the amino acid sequence of SEQ ID NO: 6; or
wherein the CD40 ligand is human CD40L comprising the sequence of SEQ ID NO: 23 or a sequence that is at least 70% identical thereto, or a CD40-binding fragment thereof; or
wherein the CD40 ligand is camelid or human CD40L comprising the sequence of SEQ ID NO: 25 or 27 or a sequence that is at least 70% identical thereto, or a CD40-binding fragment thereof.
2. The polypeptide of claim 1 , wherein the at least one receptor-binding domain, immunogenic fragment, or epitope of S1 polypeptide of Middle East respiratory syndrome coronavirus (MERS-CoV) comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 2.
3. The polypeptide of claim 1 , wherein the at least one receptor-binding domain, immunogenic fragment, or epitope of S1 polypeptide of Middle East respiratory syndrome coronavirus (MERS-CoV) comprises a sequence of SEQ ID NO: 2.
4. The polypeptide of claim 1 , wherein the at least one trimerization motif comprises the amino acid sequence of SEQ ID NO: 6.
5. The polypeptide of claim 1 , wherein the CD40 ligand is human CD40L comprising the sequence of SEQ ID NO: 23 or a sequence that is at least 70% identical thereto, or a CD40-binding fragment thereof.
6. The polypeptide of claim 1 , wherein the CD40 ligand is camelid or human CD40L comprising the sequence of SEQ ID NO: 25 or 27 or a sequence that is at least 70% identical thereto, or a CD40-binding fragment thereof.
7. The polypeptide of claim 1 that further comprises at least one peptide linker ranging from 1 to 10 amino acid residues in length between the at least one immunogenic fragment, receptor-binding domain, or epitope of S1 polypeptide of Middle East respiratory syndrome coronavirus (MERS-CoV), and/or the at least one trimerization motif, and/or the at least one ligand for CD40.
8. An immunogenic composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier, excipient and/or adjuvant.