VLP stabilized vaccine compositions
The invention is directed to compositions and methods for the stabilization of viral and bacterial vaccines. Vaccines of the invention are contained in VLPs with stabilizing agents such as, for example, sugar alcohols (e.g., sorbitol) and degraded gelatins. Preferably the gelatin has an average molecular weight of 10,000 kilodaltons or less. These vaccines have a substantially improved thermostability as well as long term stability. The invention is also directed to the manufacture of a vaccine or the invention and methods for the administration of a vaccine of the invention to patients.
1. A method of treating or preventing an infection comprising:
determining a therapeutically effective amount of a composition that has been maintained as a liquid to be administered to a mammal in need thereof, wherein:
the composition comprises virus-like particles (VLPs), an immunogenic component that is protective against the infection and a stabilizing agent,
the VLP comprises the structural components of hepatitis virus, the immunogenic component comprises a component of human papilloma virus, and the stabilizing agent comprises a degraded gelatin with an average molecular weight of ten kilodaltons or less, and
the composition has not been maintained in a non-liquid state; and
administering the therapeutically effective amount of the composition to the mammal.
2. The method of claim 1 , wherein administering is intra-muscular, intra-peritoneal, or intra-venous.
3. The method of claim 1 , wherein the patient is an infant, a toddler, an adolescent, an adult or a senior.
4. The method of claim 1 , wherein administration does not generate a general inflammatory response or local inflammation at the site of administration.
5. The method of claim 1 , wherein the stabilizing agent comprises one or more amino acids, or one or more sugar alcohols, or any combination thereof.
6. The method of claim 1 , wherein the degraded gelatin is degraded chemically or mechanically.
7. The method of claim 1 , wherein the degraded gelatin is degraded to an average molecular weight of eight kilodaltons or less.
8. The method of claim 1 , wherein the stabilizing agent further comprises a sugar alcohol.
9. The method of claim 8 , wherein the sugar alcohol comprises sorbitol.
10. The method of claim 1 , wherein the composition does not contain an aluminum compound.
11. The method of claim 1 , wherein the composition further contains a pharmaceutically acceptable carrier selected from the group consisting of alcohol, propylene glycol, fatty alcohols, triglycerides, fatty acid esters, mineral oils, liquid petrolatum, isopropylpalmitate, polyethylene ethanol, polyoxyethylene monolauriater, sodium lauryl sulfate, an anti-oxidant, a humectant, a viscosity stabilizer or modifier, a colorant or a flavoring agent.
12. A method of generating an immune response comprising:
preparing an immunogenic composition that has been maintained as a liquid comprising VLPs, an immunogenic component, and a stabilizing agent, wherein the VLP comprises the structural components of hepatitis virus, the immunogenic component comprises a component of human papilloma virus, and the stabilizing agent comprises a degraded gelatin with an average molecular weight of ten kilodaltons or less, and
wherein the immunogenic composition has not been maintained in a non-liquid state;
administering the immunogenic composition to a mammal; and
generating an immune response in the mammal.
13. The method of claim 12 , wherein the mammal is an infant, a toddler, an adolescent, an adult or a senior.
14. The method of claim 12 , wherein administration does not generate a general inflammatory response or local inflammation at the site of administration.
15. The method of claim 12 , wherein the stabilizing agent further comprises one or more amino acids, or one or more sugar alcohols, or any combination thereof.
16. The method of claim 12 , wherein the degraded gelatin is degraded to an average molecular weight of eight kilodaltons or less.
17. The method of claim 12 , wherein the immunogenic composition does not contain an aluminum compound.
18. A method of generating an immune response against an infectious agent comprising:
preparing an immunogenic composition as a liquid comprising VLPs, a stabilizing agent, and an immunogenic component, wherein the VLP comprises the structural components of hepatitis virus, the stabilizing agent comprises a degraded gelatin, the immunogenic component comprises a surface antigen of human papilloma virus, and the immunogenic composition does not contain an aluminum compound, and wherein the immunogenic composition has not been maintained in a non-liquid state;
administering the liquid immunogenic composition to a mammal, wherein the administration does not generate a general inflammatory response or local inflammation at the site of administration; and
generating an immune response against the infectious agent in the mammal.
19. The method of claim 18 , wherein the degraded gelatin is degraded chemically or mechanically.
20. The method of claim 18 , wherein the degraded gelatin is degraded to an average molecular weight of eight kilodaltons or less.
21. The method of claim 18 , wherein the degraded gelatin is degraded to an average molecular weight of five kilodaltons or less.
22. The method of claim 1 , wherein the composition is stable at temperatures from 4° C. to 50° C.
23. The method of claim 1 , wherein the composition is stable through freezing and thawing.
24. The method of claim 12 , wherein the immunogenic composition is stable at temperatures from 4° C. to 50° C.
25. The method of claim 12 , wherein the immunogenic composition is stable through freezing and thawing.
26. The method of claim 18 , wherein the immunogenic composition is stable at temperatures from 4° C. to 50° C.
27. The method of claim 18 , wherein the immunogenic composition is stable through freezing and thawing.