Compositions and methods for preventing and treating coronavirus infection—SARS-CoV-2 vaccines
The invention relates to immunogenic compositions and vaccines containing a coronavirus (e.g., Wuhan coronavirus (2019-nCoV; also referred to as SARS-CoV-2)) protein or a polynucleotide encoding a coronavirus (e.g., Wuhan coronavirus (2019-nCoV; SARS-CoV-2)) protein and uses thereof. The invention also provides methods of treating and/or preventing a coronavirus (e.g., Wuhan coronavirus (2019-nCoV; SARS-CoV-2)) infection by administering an immunogenic composition or vaccine to a subject (e.g., a human). The invention also provides methods of detecting and/or monitoring a protective anti-coronavirus (e.g., Wuhan coronavirus (2019-nCoV; SARS-CoV-2)) antibody response (e.g., anti-coronavirus antibody response, e.g., anti-2019-nCoV antibody response, e.g., anti-Spike antibody response, e.g., anti-Spike neutralizing antibody response). The present invention relates to isolated nucleic and/or recombinant nucleic acid encoding a coronavirus S protein, in particular a SARS-CoV-2 S protein, and to the coronavirus S proteins, as well as to the use of the nucleic acids and/or proteins thereof in vaccines.
1. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a 2019-NCOV Spike (S) protein comprising the following modifications to the full-length amino acid sequence of SEQ ID NO: 29:
a. stabilising mutations to proline at amino acids 986 and 987; and
b. mutations to the furin cleavage site (SEQ ID NO: 90).
2. The isolated nucleic acid molecule of claim 1 comprising a nucleotide sequence that encodes a polypeptide having at least 85% sequence identity to an amino acid sequence of SEQ ID NO: 51.
3. The isolated nucleic acid molecule of claim 1 comprising a nucleotide sequence that encodes a polypeptide having at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 51.
4. The isolated nucleic acid molecule of claim 1 comprising a nucleotide sequence that encodes a polypeptide having at least 85% sequence identity to an amino acid sequence of SEQ ID NO: 56.
5. The isolated nucleic acid molecule of claim 2 comprising a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 143, or a complementary sequence thereof.
6. The isolated nucleic acid molecule of claim 4 comprising a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 148, or a complementary sequence thereof.
7. The isolated nucleic acid molecule of claim 1 that encodes a 2019-NCOV Spike (S) protein comprising the following further modification to the full-length amino acid sequence of SEQ ID NO: 29:
c. deletion of the signal sequence.
8. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid encoding the 2019-NCOV Spike (S) protein is operably linked to a cytomegalovirus (CMV) promoter.
9. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid encoding the 2019-NCOV Spike (S) protein is operably linked to a cytomegalovirus (CMV) promoter comprising at least one tetracycline operator (TetO) motif.
10. The isolated nucleic acid molecule according to claim 9 , wherein the CMV promoter comprising at least one TetO motif comprises a nucleotide sequence of SEQ ID NO: 219.
11. An isolated 2019-NCOV Spike (S) protein comprising the following modifications to the full-length amino acid sequence of SEQ ID NO: 29:
a. stabilising mutations to proline at amino acids 986 and 987; and
b. mutations to the furin cleavage site (SEQ ID NO: 90).
12. The isolated 2019-NCOV Spike (S) protein of claim 11 comprising an amino acid sequence of SEQ ID NO: 205.
13. The isolated 2019-NCOV Spike (S) protein of claim 11 comprising an amino acid sequence having at least 85% sequence identity to an amino acid sequence of SEQ ID NO: 51.
14. The isolated 2019-NCOV Spike (S) protein of claim 11 comprising an amino acid sequence having at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 51.
15. The isolated 2019-NCOV Spike (S) protein of claim 11 comprising an amino acid sequence having at least 85% sequence identity to an amino acid sequence of SEQ ID NO: 56.
16. The isolated 2019-NCOV Spike (S) protein of claim 11 comprising the following further modification to the full-length amino acid sequence of SEQ ID NO: 29:
c. deletion of the signal sequence.
17. An isolated vector comprising one or more of the nucleic acid molecules of claim 1 .
18. The vector of claim 17 , wherein the vector is an adenovirus of serotype 26.
19. A composition comprising the nucleic acid molecule of claim 1 .
20. The composition of claim 19 , further comprising a pharmaceutically acceptable carrier, excipient, or diluent.
21. The composition of claim 19 for use in active immunization for the prevention of coronavirus disease-2019 (COVID-19) in adults 18 years of age and older.
22. A method of active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older, comprising administering to the subject the composition of claim 19 .
23. The method of claim 22 , comprising administering the composition in a one dose regimen.
24. The method of claim 22 , comprising administering the composition in a two dose regimen, wherein the doses are administered about 1, 2, or 3 months apart.
25. The method of claim 22 , wherein the composition is administered at a dose of 5×10 10 vp per dose.
26. A method of manufacturing an immunogenic composition for preventing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older, said method comprising the steps of:
(a) admixing at least one of the nucleic acid molecule of claim 1 with a pharmaceutically acceptable carrier, excipient, or diluent to form the immunogenic composition; and
(b) placing the immunogenic composition in a container.
27. A kit comprising:
(a) a first container comprising at least one of the nucleic acid molecule of claim 1 ;
(b) instructions for use thereof; and optionally
(c) a second container comprising a pharmaceutically acceptable carrier, excipient, or diluent.
28. The isolated nucleic acid molecule of claim 8 , wherein the CMV promoter is a CMV immediate early promoter.