CpG-adjuvanted SARS-CoV-2 virus vaccine
Described herein are CpG-adjuvanted SARS-CoV-2 vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.
1. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunogenic composition comprising i) an inactivated SARS-CoV-2 whole virus particle comprising an S protein having at least 96% amino acid sequence identity to SEQ ID NO: 3; ii) a CpG-containing oligodeoxynucleotide (CpG-ODN) consisting of the sequence of SEQ ID NO: 4; and iii) an alum adjuvant;
wherein the immunogenic composition induces neutralizing antibodies against SARS-CoV-2 in a subject immunized intramuscularly with the immunogenic composition; and
wherein the immunogenic composition does not induce antibody-dependent enhancement of SARS-CoV-2-associated disease in the subject.
2. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the S protein has at least 99% amino acid sequence identity to SEQ ID NO: 3.
3. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the alum adjuvant is aluminium hydroxide.
4. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the alum:CpG-ODN (w/w) ratio in the immunogenic composition is between about 1:3 and about 3:1.
5. The SARS-CoV-2 immunogenic composition according to claim 4 , wherein the alum:CpG-ODN (w/w) ratio in the immunogenic composition is about 1:2.
6. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the alum content of the immunogenic composition is between about 0.8 to about 1.2 mg/mL.
7. The SARS-CoV-2 immunogenic composition according to claim 6 , wherein the alum content of the immunogenic composition is about 1 mg/mL, and wherein the immunogenic composition is delivered in a volume of 0.5 mL.
8. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the CpG-ODN content of the immunogenic composition is between about 1.5 to about 2.5 mg/mL.
9. The SARS-CoV-2 immunogenic composition according to claim 8 , wherein the CpG-ODN content of the immunogenic composition is about 2 mg/mL, and wherein the immunogenic composition is delivered in a volume of 0.5 mL.
10. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the amount of inactivated SARS-CoV-2 whole virus particles per 0.5 mL dose in the immunogenic composition is between about 0.25 and about 2.5 mAU (milli-absorption units×minutes) as assessed by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC).
11. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the amount of inactivated SARS-CoV-2 whole virus particles per 0.5 mL dose in the immunogenic composition is 35 Antigen Units as determined by SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) assay.
12. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the amount of free (unbound) CpG-ODN in the immunogenic composition is about 80% to about 90% (w/w), based on the total amount of CpG-ODN in the immunogenic composition.
13. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the whole virus particle is a beta-propiolactone-inactivated SARS-CoV-2 particle.
14. The SARS-CoV-2 immunogenic composition according to claim 1 ,
wherein the inactivated SARS-CoV-2 whole virus particle comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 9; or (ii) having at least 90% sequence identity to SEQ ID NO: 9; and/or
wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 18; or (ii) having at least 90% sequence identity to SEQ ID NO: 18; and/or
wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 22; or (ii) having at least 90% sequence identity to SEQ ID NO: 22.
15. The SARS-CoV-2 immunogenic composition according to claim 14 ,
wherein the inactivated SARS-CoV-2 whole virus particle comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 9; or (ii) having at least 95% sequence identity to SEQ ID NO: 9; and/or
wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 18; or (ii) having at least 95% sequence identity to SEQ ID NO: 18; and/or
wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 22; or (ii) having at least 95% sequence identity to SEQ ID NO: 22.
16. The SARS-CoV-2 immunogenic composition according to claim 15 ,
wherein the inactivated SARS-CoV-2 whole virus particle comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 9; or (ii) having at least 99% sequence identity to SEQ ID NO: 9; and/or
wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 18; or (ii) having at least 99% sequence identity to SEQ ID NO: 18; and/or
wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 22; or (ii) having at least 99% sequence identity to SEQ ID NO: 22.
17. A kit comprising a SARS-CoV-2 immunogenic composition according to claim 1 , and further comprising a second immunogenic composition.
18. The kit according to claim 17 , wherein the second immunogenic composition is another SARS-CoV-2 virus immunogenic composition, a Japanese encephalitis virus immunogenic composition, a Zika virus immunogenic composition, a Dengue virus immunogenic composition, an influenza virus immunogenic composition, or a Chikungunya virus immunogenic composition.
19. A method of producing a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunogenic composition, comprising:
(a) producing SARS-CoV-2 whole virus particles comprising an S protein having at least 96% amino acid sequence identity to SEQ ID NO: 3;
(b) inactivating the SARS-CoV-2 whole virus particles to obtain inactivated SARS-CoV-2 whole virus particles; and
(c) incorporating the inactivated SARS-CoV-2 whole virus particles in a immunogenic composition comprising a CpG-containing oligodeoxynucleotide (CpG-ODN) and an alum adjuvant, wherein said CpG-ODN consists of the sequence of SEQ ID NO: 4;
wherein the immunogenic composition induced neutralizing antibodies against SARS-CoV-2 in a subject immunized intramuscularly with the immunogenic composition; and
wherein the immunogenic composition does not induce antibody-dependent enhancement of SARS-CoV-2-associated disease in the subject.
20. The method according to claim 19 , wherein said alum adjuvant is aluminium hydroxide.
21. The method according to claim 19 , wherein the alum:CpG-ODN (w/w) ratio in the immunogenic composition is between about 1:3 and about 3:1.
22. The method according to claim 21 , wherein the alum:CpG-ODN (w/w) ratio in the immunogenic composition is about 1:2.
23. The method according to claim 19 , wherein the alum content of the immunogenic composition is between about 0.8 to about 1.2 mg/mL.
24. The method according to claim 23 , wherein the alum content of the immunogenic composition is about 1 mg/mL, and wherein the immunogenic composition is delivered in a volume of 0.5 mL.
25. The method according to claim 19 , wherein the CpG-ODN content of the immunogenic composition is between about 1.5 to about 2.5 mg/mL.
26. The method according to claim 25 , wherein the CpG-ODN content of the immunogenic composition is about 2 mg/mL, and wherein the immunogenic composition is delivered in a volume of 0.5 mL.
27. The method according to claim 19 , wherein the amount of inactivated SARS-CoV-2 whole virus particles per dose in the immunogenic composition is 35 Antigen Units as determined by SARS-CoV-2 ELISA assay.
28. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the inactivated SARS-CoV-2 whole virus particle comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 9; or (ii) having at least 95% sequence identity to SEQ ID NO: 9.
29. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 18; or (ii) having at least 95% sequence identity to SEQ ID NO: 18.
30. The SARS-CoV-2 immunogenic composition according to claim 1 , wherein the immunogenic composition comprises an additional SARS-CoV-2 particle that comprises an RNA sequence corresponding to a DNA sequence (i) of SEQ ID NO: 22; or (ii) having at least 95% sequence identity to SEQ ID NO: 22.