Vaccines formed by virus and antigen conjugation
Disclosed herein are methods of forming compounds and exemplary stable compounds in the nature of a conjugated compound at refrigerated or room temperature, which in some embodiments comprises an antigen and virus particle mixed in a conjugation reaction to form a conjugate mixture, such that the conditions and steps of forming these products allow for use of the conjugate mixture as a vaccine, including but not limited to use as a vaccine against various pathogens including for treatment of diseases caused by novel coronaviruses (including SARS-COV 2).
1. A multivalent vaccine, comprising:
a first antigen comprising an influenza hemagglutinin antigen (HA);
a second antigen; and
a carrier comprising a virus particle having surface lysine residues; wherein the first antigen and the second antigen chemically associate with the surface lysine residues.
2. The multivalent vaccine of claim 1 , wherein the second antigen is an influenza HA other than the first antigen.
3. The multivalent vaccine of claim 1 , wherein the vaccine comprises two or more type A hemagglutinin antigens (HAs) and two or more type B HAs.
4. The multivalent vaccine of claim 1 , wherein the second antigen comprises a receptor binding domain of a coronavirus.
5. The multivalent vaccine of claim 4 , wherein the coronavirus is chosen from the group consisting of SARS-CoV-1 and SARS-CoV-2.
6. The multivalent vaccine of claim 5 , wherein the vaccine comprises two or more type A hemagglutinin antigens (HAs) and two or more type B HAs.
7. The multivalent vaccine of claim 1 , wherein the virus particle is a virus.
8. The multivalent vaccine of claim 7 , wherein the virus is a tobacco mosaic virus.
9. The multivalent vaccine of claim 1 , wherein when the vaccine is placed in an unrefrigerated environment at a storage temperature for a time period, an integrity or a concentration of the vaccine at the end of the time period is at least 90% of an initial integrity or an initial concentration of the vaccine, wherein the time period is at least 42 days after a release date of the vaccine.
10. The multivalent vaccine of claim 9 , wherein the storage temperature is at least 20° C.
11. A virus-antigen conjugate, comprising a virus and at least one antigen, wherein the at least one antigen comprises a fusion peptide having a first peptide which comprises a receptor binding domain of a pathogen, and a second peptide wherein the fusion peptide is chemically linked with the virus, and wherein the second peptide is a fragment crystallizable (Fc) region of an antibody capable of binding to a Fc receptor.
12. The conjugate of claim 11 , wherein the conjugate is multivalent, and further comprises at least one influenza hemagglutinin antigen (HA) chosen from the group consisting of type A HA and type B HA.
13. The conjugate of claim 11 , wherein the Fc region is an Fc domain of an IgG1 antibody.
14. The conjugate of claim 13 , further comprising a hinge portion linking the first peptide and the second peptide, wherein the hinge portion contains an amino acid sequence as set forth in SEQ ID NO: 3.
15. The conjugate of claim 14 , wherein the pathogen is a coronavirus having said receptor binding domain.
16. The conjugate of claim 15 , wherein the first peptide contains an amino acid sequence as set forth in SEQ ID NO: 2.
17. The conjugate of claim 15 , wherein the first peptide contains an amino acid sequence as set forth in SEQ ID NO: 8.
18. The conjugate of claim 11 , wherein the virus is a tobacco mosaic virus.
19. The conjugate of claim 18 , wherein the tobacco mosaic virus comprises a N-terminal lysine residue.
20. An antigen, comprising:
a fusion peptide having a first peptide which comprises a receptor binding domain of a coronavirus, and a second peptide wherein the fusion peptide is capable of being chemically linked with a virus particle,
wherein the second peptide is a fragment crystallizable (Fc) region of an antibody capable of binding to a Fc receptor.
21. The antigen of claim 20 , wherein when the antigen is placed in an unrefrigerated environment at a storage temperature for a time period, an integrity or a concentration of the antigen at the end of the time period is at least 90% of an initial integrity or an initial concentration of the antigen, wherein the time period is at least 42 days after a release date of the conjugate.
22. The antigen of claim 21 , wherein the storage temperature is at least 20° C.
23. The antigen of claim 22 , wherein the first peptide contains an amino acid sequence as set forth in SEQ ID NO: 2.
24. The antigen of claim 22 , wherein the first peptide contains an amino acid sequence as set forth in SEQ ID NO: 8.