Prefusion coronavirus spike proteins and their use
Coronavirus S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the coronavirus S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to coronavirus in a subject. In additional embodiments, the therapeutically effective amount of the coronavirus S ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing coronavirus infection.
1. A nucleic acid molecule encoding a recombinant coronavirus S protein comprising two proline substitutions between the heptad repeat 1 (HR1) and the central helix of the S protein.
2. The nucleic acid molecule of claim 1 , wherein the coronavirus is a betacoronavirus.
3. The nucleic acid molecule of claim 1 , wherein the coronavirus is one of MERS-CoV, SARS-CoV, NL63-CoV, 229E-CoV, 0C43-CoV, HKU1-CoV, WIV1-CoV, MHV, HKU9-CoV, PEDV-CoV, or SDCV.
4. The nucleic acid molecule of claim 1 , wherein the recombinant coronavirus S protein further comprises a mutation to inhibit cleavage of a S1/S2 protease cleavage site.
5. The nucleic acid molecule of claim 1 , operably linked to a promoter.
6. An immunogenic composition comprising the nucleic acid molecule of claim 1 , and a pharmaceutically acceptable carrier.
7. A method for generating an immune response to a coronavirus S protein in a subject, comprising administering to the subject an effective amount of the nucleic acid molecule of claim 1 to generate the immune response.
8. The method of claim 7 , wherein the immune response inhibits infection with the coronavirus.
9. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is an mRNA molecule.
10. The nucleic acid molecule of claim 9 , wherein the coronavirus is a betacoronavirus.
11. The nucleic acid molecule of claim 9 , wherein the coronavirus is one of MERS-CoV, SARS-CoV, NL63-CoV, 229E-CoV, OC43-CoV, HKU1-CoV, WIV1-CoV, MHV, HKU9-CoV, PEDV-CoV, or SDCV.
12. The nucleic acid molecule of claim 9 , wherein the recombinant coronavirus S protein further comprises a mutation to inhibit cleavage of a S1/S2 protease cleavage site.
13. An immunogenic composition comprising the nucleic acid molecule of claim 9 , and a pharmaceutically acceptable carrier.
14. A method for generating an immune response to a coronavirus S protein in a subject, comprising administering to the subject an effective amount of the nucleic acid molecule of claim 9 to generate the immune response.
15. The method of claim 14 , wherein the immune response inhibits infection with the coronavirus.