Multivalent VLP conjugates
The invention is directed to vaccines comprising capsular polysaccharides conjugated to one or more components of virus like particles (VLP), and methods for the administration of and methods for the manufacture of vaccines of the invention. Preferably vaccines of the invention generate a therapeutically effective response in an individual in need thereof to multiple strains and/or serotypes of the same or of different infectious agents. Preferably such vaccines generate a therapeutically effective immune response to all pathogenic strains and/or serotypes of the same infectious agent. In particular, the invention is directed to methods and compositions for the cost efficient administration of a vaccine to a patient in need thereof exposing the patient's immune system to only the immunogenic components that are likely to be beneficial for the generation of a protective immunological response, both efficacy and safety are increased and cost effectively.
1. A vaccine against multiple serotypes of an infectious agent comprising virus like particles obtained or derived from hepatitis virus coupled to multiple polysaccharides each polysaccharide representing a serotype of the infectious agent with little to no misassembly or misfolding, wherein the infectious agent is Streptococcus pneumoniae.
2. The vaccine of claim 1 , wherein the multiple polysaccharides are covalently coupled via conjugation to one or more components of the virus like particles.
3. The vaccine of claim 2 , wherein the conjugation involves coupling via a cyanylating agent.
4. The vaccine of claim 3 , wherein the cyanylating agent comprises 1-cyano-4-(dimethylamino)-pyridinium tetrafluoroborate (CDAP), 1-cyanobenzotriazole (1-CBT), 2-cyanopyridazine-3 (2H)-One (2-CPO), 1-cyanoimidazole (1-CI), 1-cyano-4-pyrrolidinopyridinium tetrafluorborate (CPPT) or a combination thereof.
5. The vaccine of claim 1 , wherein the multiple polysaccharides are obtained and/or derived from one or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
6. The vaccine of claim 1 , wherein the multiple polysaccharides are obtained and/or derived from two or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
7. The vaccine of claim 1 , wherein the multiple polysaccharides are obtained and/or derived from the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
8. The vaccine of claim 1 , which does not require an adjuvant to generate a therapeutically effective response.
9. The vaccine of claim 1 , further comprising an adjuvant.
10. The vaccine of claim 9 , wherein the adjuvant comprises aluminum hydroxide with phosphate buffer.
11. The vaccine of claim 1 , which upon administration to a patient, generates a therapeutically effective immune response against the infectious agent.
12. The vaccine of claim 11 , wherein the therapeutically effective immune response comprises protection to an individual against a subsequent infection of the infectious agent and/or therapeutic treatment to an individual infected by the infectious agent.
13. The vaccine of claim 11 , wherein the therapeutically effective immune response provides protection against infection by multiple serotypes of the infectious agent.
14. The vaccine of claim 11 , wherein the therapeutically effective immune response comprises a humoral and/or a cellular immune response against the infectious agent.
15. The vaccine of claim 6 , wherein the multiple polysaccharides are obtained and/or derived from five or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
16. The vaccine of claim 15 , wherein the multiple polysaccharides are obtained and/or derived from ten or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
17. The vaccine of claim 16 , wherein the multiple polysaccharides are obtained and/or derived from fifteen or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
18. The vaccine of claim 17 , wherein the multiple polysaccharides are obtained and/or derived from twenty or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.
19. The vaccine of claim 18 , wherein the multiple polysaccharides are obtained and/or derived from twenty three or more of the serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F of Streptococcus pneumoniae.