Vaccine compositions
Provided herein are vaccine compositions for example in a dry powder form for intranasal delivery, and their preparation methods. Also provided are methods of using vaccine compositions, for example in stimulating mucosal or systemic immune responses by delivering the vaccine compositions intranasally.
1. A vaccine composition, wherein the vaccine composition is in a solid form and comprises:
an antigen;
a first saccharide, wherein the first saccharide is trehalose;
a second saccharide, wherein the second saccharide is mannitol; and
a third saccharide that comprises microcrystalline cellulose, wherein: a weight ratio of the first saccharide to the second saccharide is from about 1:1 to about 1:5, or a molar ratio of the first saccharide to the second saccharide is from about 1:2 to about 1:10.
2. The vaccine composition of claim 1 , which, when administered intranasally to a human, produces a serum immune response.
3. The vaccine composition of claim 1 , which, when administered intranasally to a human, stimulates a production of a serum Immunoglobulin G (IgG) antibody.
4. The vaccine composition of claim 1 , which, when administered intranasally to a human, produces a mucosal immune response.
5. The vaccine composition of claim 1 , which, when administered intranasally to a human, stimulates a production of a mucosal secretory Immunoglobulin A (sIgA) antibody.
6. The vaccine composition of claim 1 , which, when administered intranasally to a human, produces a cellular immune response.
7. The vaccine composition of claim 1 , having the weight ratio of the first saccharide to the second saccharide that is about: 1:1, 1:2, 1:3, or 1:4.
8. The vaccine composition of claim 1 , having the molar ratio of the first saccharide to the second saccharide which is about: 1:1, 2:3, 1:2, or 2:7.
9. The vaccine composition of claim 1 , wherein at least 80% (w/w) of the first saccharide is in an amorphous form as measured by an X-ray powder diffraction analysis.
10. The vaccine composition of claim 1 , wherein at least 20% (w/w) of the second saccharide is in a crystal form as measured by an X-ray powder diffraction analysis.
11. The vaccine composition of claim 1 , wherein the microcrystalline cellulose has an average particle size from about 10 microns to about 100 microns as measured by sifting, sieving, or laser diffraction.
12. The vaccine composition of claim 1 , wherein the antigen comprises a viral antigen, a bacterial antigen, or a combination thereof.
13. The vaccine composition of claim 1 , wherein the antigen comprises live attenuated virus, whole inactivated virus, split virus, subunit antigen, virosome, antigenic protein, antigenic peptide, virus-like particle with antigenic protein, virus-like particle with antigenic peptide, cold-adapted live virus, killed whole bacteria, attenuated bacteria, bacterial toxoid, bacterial antigenic polysaccharide, nucleotide, phage, or any combination thereof.
14. The vaccine composition of claim 1 , wherein the antigen comprises influenza virus, respiratory syncytial virus, Rhinovirus, Coronavirus, Adenovirus, metapneumovirus, bocavirus, parainfluenza virus, measles virus, rubella virus, varicella zoster virus, herpes simplex virus, human herpes virus, Parvovirus B19, Enterovirus, mumps virus, or any combination thereof.
15. The vaccine composition of claim 1 , wherein the antigen comprises human papillomavirus, poliovirus, Rotavirus, Norwalk virus, sapovirus, Astrovirus, or any combination thereof.
16. The vaccine composition of claim 1 , wherein the antigen comprises an influenza split virus.
17. The vaccine composition of claim 1 , wherein the antigen comprises an influenza virosome.
18. The vaccine composition of claim 1 , wherein the antigen comprises a whole inactivated influenza virus.
19. The vaccine composition of claim 1 , wherein the vaccine composition further comprises an adjuvant.
20. A vaccine composition of claim 1 , for intranasal administration.
21. A device that comprises a vaccine composition of claim 1 .
22. The vaccine composition of claim 1 , wherein a total amount of the first saccharide and the second saccharide is from about 45 mg to about 150 mg.
23. The vaccine composition of claim 1 , wherein a total amount of the first saccharide and the second saccharide is about 50 mg, about 75 mg, or about 100 mg.
24. The vaccine composition of claim 1 , having the weight ratio of the first saccharide to the second saccharide that is from about 1:1 to about 1:4.
25. The vaccine composition of claim 1 , wherein: the antigen is a split virus antigen, the first saccharide and the second saccharide have a weight ratio of from about 1:1 to about 1:4, and a total amount of the first saccharide and the second saccharide is about 100 mg.
26. The vaccine composition of claim 1 , wherein: the antigen is a virosome antigen, the first saccharide and the second saccharide have a weight ratio of about 1:1, and a total amount of the first saccharide and the second saccharide is about 100 mg.
27. The vaccine composition of claim 1 , wherein: the antigen is a virosome antigen, the first saccharide and the second saccharide have a weight ratio of from about 1:1 to about 1:2, and a total amount of the first saccharide and the second saccharide is about 75 mg.
28. The vaccine composition of claim 1 , wherein: the antigen is a virosome antigen, the first saccharide and the second saccharide have a weight ratio of about 1:2, and a total amount of the first saccharide and the second saccharide is about 50 mg.
29. The vaccine composition of claim 1 , wherein: the antigen is a whole inactive virus antigen, the first saccharide and the second saccharide have a weight ratio of about 1:1, and a total amount of the first saccharide and the second saccharide is about 100 mg.
30. The vaccine composition of claim 1 , wherein the vaccine composition is in a solid form of cake.
31. The vaccine composition of claim 1 , wherein the vaccine composition is in a solid form of powder.
32. The vaccine composition of claim 1 , having the weight ratio of the first saccharide to the second saccharide from about 1:1 to about 1:5.
33. The vaccine composition of claim 1 , having the molar ratio of the first saccharide to the second saccharide from about 1:2 to about 1:10.