Coronavirus disease (COVID-19) vaccine
The present invention includes a vaccine comprising a SARS-CoV-2 spike protein (S) or portion thereof, and methods of use thereof.
1. An isolated nucleic acid encoding a recombinant virus comprising a SARS-CoV-2 spike protein (S) or a portion thereof, wherein the virus is a rabies virus, a vesicular stomatitis virus (VSV), or a measles virus, and wherein the portion of the SARS-CoV-2 spike protein (S) comprises a receptor binding site of the SARS-CoV-2 spike protein (S).
2. The isolated nucleic acid of claim 1 , wherein the virus is a rhabdovirus.
3. The isolated nucleic acid of claim 1 , wherein the portion of the SARS-CoV-2 spike protein (S) is a S1 domain.
4. The isolated nucleic acid of claim 1 , wherein the nucleic acid comprises (a) a sequence encoding at least a portion of the genome of a measles virus and (b) a sequence encoding the SARS-CoV-2 spike protein (S) or the portion thereof.
5. The isolated nucleic acid of claim 4 , wherein the sequence encoding the SARS-CoV-2 spike protein (S) or portion thereof is inserted into positions 2, 3, or 6 of the genome of the measles virus.
6. The isolated nucleic acid of claim 1 , wherein the nucleic acid comprises (a) a sequence encoding at least a portion of the genome of a rabies virus and (b) a sequence encoding the SARS-CoV-2 spike protein (S) or the portion thereof.
7. The isolated nucleic acid of claim 6 , wherein the at least a portion of the genome of the rabies virus comprises an N gene and a P gene, and the sequence encoding the SARS-CoV-2 spike protein (S) or portion thereof is inserted into a position between the N gene and P gene.
8. The isolated nucleic acid of claim 1 , wherein the nucleic acid comprises (a) a sequence encoding at least a portion of the genome of a vesicular stomatitis virus (VSV), and (b) a sequence encoding the SARS-CoV-2 spike protein (S) or the portion thereof.
9. The isolated nucleic acid of claim 1 , wherein the protein comprising a SARS-CoV-2 spike protein (S) or a portion thereof is a fusion protein comprising a glycoprotein (G) or a portion thereof and the SARS-CoV-2 spike protein (S) or the portion thereof.
10. The isolated nucleic acid of claim 9 , wherein the fusion protein comprises a glycoprotein (G) or portion thereof fused to the S1 domain of a SARS-CoV-2 spike protein (S).
11. The isolated nucleic acid of claim 1 , wherein the nucleic acid comprises the sequence set forth in any one of SEQ ID NOs: 1-27.
12. The isolated nucleic acid of claim 11 , wherein the nucleic acid comprises the sequence set forth in SEQ ID NO: 2.
13. The isolated nucleic acid of claim 1 , wherein the SARS-CoV-2 spike protein (S) comprises the sequence of SEQ ID NO: 28; or a sequence comprising at least 98%, but not 100%, sequence identity to the sequence of SEQ ID NO: 28.
14. A vector comprising the nucleic acid of claim 1 .
15. A vaccine comprising the isolated nucleic acid of claim 1 , and a pharmaceutically acceptable carrier.
16. The vaccine of claim 15 , further comprising an adjuvant.
17. The vaccine of claim 16 , wherein the adjuvant is MPLA 3D(6-acyl) in 2% squalene.
18. A method of generating an immune response against a SARS-CoV-2 virus in a subject in need thereof, the method comprising administering to the subject an effective amount of the vaccine of claim 15 .
19. A method of vaccinating a subject against a SARS-CoV-2 virus, the method comprising administering to the subject an effective amount of the vaccine of claim 15 .
20. A method of treating and/or preventing a disease or disorder associated with a SARS-CoV-2 virus in a subject in need thereof, the method comprising administering to the subject an effective amount of the vaccine of claim 15 .