Vaccine compositions for the treatment of coronavirus
The present disclosure provides compositions and methods useful for preventing and/or treating coronavirus infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more coronavirus epitopes, such as, for example, from SARS-Cov-2 spike protein.
1. An immunogenic composition comprising a virus-like particle (VLP) comprising:
a first polypeptide that is a gag protein found in murine leukemia virus (MLV) having at least 95% identity with the amino acid sequence of SEQ ID NO:1;
at least one additional polypeptide which is a spike glycoprotein from a beta coronavirus; and
a pharmaceutically acceptable carrier.
2. The immunogenic composition of claim 1 wherein the at least one additional polypeptide is a spike glycoprotein from SARS-CoV-2, SARS-CoV or MERS-CoV.
3. The immunogenic composition of claim 2 wherein the spike glycoprotein is a wild type protein.
4. The immunogenic composition of claim 2 wherein the spike glycoprotein is a modified protein.
5. The immunogenic composition of claim 2 comprising two spike glycoproteins.
6. The immunogenic composition of claim 2 comprising three spike glycoproteins.
7. The immunogenic composition of claim 4 wherein the modified protein has a deletion at a furin cleavage site.
8. The immunogenic composition of claim 7 wherein the modified protein has a transmembrane domain from VSV.
9. The immunogenic composition of claim 4 wherein the modified protein has a lysine residue and a valine residue replaced with proline residues.
10. The immunogenic composition of claim 9 wherein the modified protein has a transmembrane domain from VSV.
11. The immunogenic composition of claim 4 wherein the modified protein has a lysine residue and a valine residue replaced with proline residues and has a deletion at a furin cleavage site.
12. The immunogenic composition of claim 4 wherein the modified protein has a lysine residue and a valine residue replaced with proline residues and has a deletion at a furin cleavage site and has a transmembrane domain from VSV.
13. The immunogenic composition of claim 1 , wherein the additional polypeptide has an amino acid sequence sequence of SEQ ID NO: 22.
14. The immunogenic composition of claim 1 , further comprising an adjuvant.
15. The immunogenic composition of claim 14 , wherein the adjuvant is selected from the group consisting of cytokines, gel-type adjuvants, microbial adjuvants, oil-emulsion and emulsifier-based adjuvants, particulate adjuvants, synthetic adjuvants, polymer adjuvants, and/or combinations thereof.
16. The immunogenic composition of claim 15 , wherein the particulate adjuvant is an aluminum salt.
17. The immunogenic composition of claim 1 , wherein the VLP is produced by co-transfecting a host cell with a first vector comprising a nucleotide sequence of SEQ ID NO: 3 and a second vector comprising a nucleotide sequence of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24 or 27; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.
18. The immunogenic composition of claim 1 , wherein the VLP is produced by co-transfecting a host cell with a first vector comprising a nucleotide sequence of SEQ ID NO: 3, a second vector comprising a nucleotide sequence of SEQ ID NO: 6; a third vector comprising a nucleotide sequence of SEQ ID NO: 9 and a fourth vector comprising a nucleotide sequence of SEQ ID NO: 12; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.
19. The immunogenic composition of claim 1 , wherein the VLP is produced by co-transfecting a host cell with a first vector comprising a nucleotide sequence of SEQ ID NO: 3 and a second vector comprising a nucleotide sequence of SEQ ID NO: 25; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.
20. A method of treating a subject having or at risk for coronavirus infection, comprising administering to the subject the pharmaceutical composition of claim 1 .