Immunogenic compositions containing microparticles comprising adsorbed toxoid and polysaccharide-containing antigens
Immunogenic compositions comprising microparticles with adsorbed toxoid antigen and/or polysaccharide-containing antigen are disclosed. The immunogenic microparticle compositions comprise (a) polymer microparticles comprising a biodegradable polymer; (b) an antigen adsorbed to the microparticles selected from (i) a toxoid antigen, such as a tetanus toxoid, a diphtheria toxoid, or a combination thereof, and/or (ii) a polysaccharide containing antigen, such as a Hib polysaccharide antigen, a Hib conjugate antigen comprising polysaccharide and polypeptide regions, a meningococcal polysaccharide antigen, a meningococcal conjugate antigen comprising polysaccharide and polypeptide regions, a pneumococcal polysaccharide antigen, and a pneumococcal conjugate antigen comprising polysaccharide and polypeptide regions or a combination thereof; and (c) a pharmaceutically acceptable excipient. The biodegradable polymer can be, for example, a polymer selected from a poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and a polycyanoacrylate. Also disclosed are methods of immunization against infection by a pathogenic organisms and methods stimulating immune responses, which comprise administering such compositions to host animals. Methods of producing such microparticle compositions are also disclosed which comprise forming a water-in-oil-in-water emulsion that contains water, organic solvent and biodegradable polymer, followed by removal of the organic solvent from the emulsion to form microparticles, after which toxoid and/or polysaccharide containing antigens are adsorbed on the microparticles.
1. An immunogenic composition comprising: (a) polymer microparticles comprising a biodegradable polymer selected from a poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, a polycyanoacrylate, and combinations thereof and an anionic surfactant; (b) a polysaccharide-containing antigen, a diphtheria toxoid antigen and a tetanus toxoid antigen adsorbed to the polymer microparticles; and (c) a pharmaceutically acceptable excipient.
2. The immunogenic composition of claim 1 , further comprising an additional antigen.
3. The immunogenic composition of claim 2 , wherein the additional antigen is adsorbed to the surface of the microparticles.
4. The immunogenic composition of claim 2 , wherein the additional antigen is a polypeptide-containing antigen.
5. The immunogenic composition of claim 2 , wherein the additional antigen is an additional polysaccharide-containing antigen.
6. The immunogenic composition of claim 2 , wherein the additional antigen is an additional conjugate antigen comprising polysaccharide and polypeptide regions.
7. The immunogenic composition of claim 2 , wherein the additional antigen is a polynucleotide-containing antigen.
8. The immunogenic composition of claim 2 , wherein the additional antigen is derived from a tumor cell.
9. The immunogenic composition of claim 2 , wherein the additional antigen is derived from a pathogenic organism.
10. The immunogenic composition of claim 9 , wherein the pathogenic organism is selected from a virus, a bacterium, a fungus and a parasite.
11. The immunogenic composition of claim 9 , wherein the pathogenic organism is selected from hepatitis virus, varicella, poliovirus, measles, mumps, rubella, influenza virus, Neisseria meningitides , pertussis, Haemophilus influenzae type b, HIV and Streptococcus pneumoniae.
12. The immunogenic composition of claim 9 , wherein the pathogenic organism is pertussis.
13. The immunogenic composition of claim 12 , wherein the composition comprises a hepatitis virus antigen.
14. The immunogenic composition of claim 13 , wherein the composition comprises an antigen selected from a Haemophilus influenzae type b antigen, a poliovirus antigen, a Neisseria meningitidis antigen, and a Streptococcus pneumoniae antigen.
15. The immunogenic composition of claim 12 , wherein the composition comprises a Haemophilus influenzae type b antigen.
16. The immunogenic composition of claim 15 , wherein the composition comprises an antigen selected from a hepatitis virus antigen, a poliovirus antigen, a Neisseria meningitides antigen and a Streptococcus pneumoniae antigen.
17. The immunogenic composition of claim 12 , wherein the composition comprises a poliovirus antigen.
18. The immunogenic composition of claim 17 , wherein the composition comprises an antigen selected from a hepatitis virus antigen, a Haemophilus influenzae type b antigen, a Neisseria meningitidis antigen and a Streptococcus pneumoniae antigen.
19. The immunogenic composition of claim 12 , wherein the composition comprises a Neisseria meningitidis antigen.
20. The immunogenic composition of claim 19 , wherein the composition comprises an antigen selected from a hepatitis virus antigen, a Haemophilus influenzae type b antigen, a poliovirus antigen, and a Streptococcus pneumoniae antigen.
21. The immunogenic composition of claim 12 , wherein the composition comprises a Streptococcus pneumoniae antigen.
22. The immunogenic composition of claim 21 , wherein the composition comprises an antigen selected from a hepatitis virus antigen, a Haemophilus influenzae type b antigen, a poliovirus antigen and a Neisseria meningitidis antigen.
23. The immunogenic composition of claim 9 , wherein the additional antigen is a killed or attenuated pathogenic organism.
24. The immunogenic composition of claim 1 , wherein the biodegradable polymer is a poly(α-hydroxy acid).
25. The immunogenic composition of claim 1 , further comprising a supplemental immunological adjuvant.
26. The immunogenic composition of claim 25 , wherein the supplemental immunological adjuvant is adsorbed to the surface of the microparticles.
27. The immunogenic composition of claim 25 , wherein the supplemental immunological adjuvant is entrapped within the microparticles.
28. The immunogenic composition of claim 25 , wherein the supplemental immunological adjuvant is selected from CpG oligonucleotides, double-stranded RNA, E. coli heat-labile toxins, liposaccharide phosphate compounds, liposaccharide phosphate mimetics, and submicron emulsions that comprise squalene, a sorbitan ester and a polyoxyethylene sorbitan ester.
29. The immunogenic composition of claim 1 , wherein the polysaccharide containing antigen adsorbed to the microparticles is selected from a Hib polysaccharide antigen, a Hib conjugate antigen, a meningococcal polysaccharide antigen, a meningococcal conjugate antigen, a pneumococcal polysaccharide antigen, and a pneumococcal conjugate antigen.
30. The immunogenic composition of claim 29 , wherein the polysaccharide containing antigen is a meningococcal conjugate antigen.
31. The immunogenic composition of claim 30 , wherein the meningococcal conjugate antigen is a meningitis C conjugate antigen.
32. The immunogenic composition of claim 1 , wherein said polysaccharide-containing antigen is selected from a Hib polysaccharide antigen, a meningococcal polysaccharide antigen and a pneumococcal polysaccharide antigen.
33. The immunogenic composition of claim 1 , wherein said polysaccharide-containing antigen is selected from a Hib conjugate antigen, a meningococcal conjugate antigen, and a pneumococcal conjugate antigen.
34. The immunogenic composition of claim 1 , wherein said polysaccharide-containing antigen is a Hib conjugate antigen.
35. The immunogenic composition of claim 1 , wherein said anionic surfactant is selected from sodium dodecyl sulfate, sodium lauryl sulfate and dioctyl sodium sulfosuccinate.
36. The immunogenic composition of claim 1 , wherein said anionic surfactant is dioctyl sodium sulfosuccinate.
37. The immunogenic composition of claim 1 , wherein said anionic surfactant is dioctyl sodium sulfosuccinate and wherein said biodegradable polymer is a poly(lactide-co-glycolide) having a lactide:glycolide molar ratio ranging from 40:60 to 60:40.
38. The immunogenic composition of claim 1 , wherein said polysaccharide-containing antigen is adsorbed to said microparticles independently of said diphtheria and tetanus toxoid antigens.
39. The immunogenic composition of claim 31 , wherein said polysaccharide-containing antigen is a meningococcal conjugate antigen that is adsorbed to said microparticles in the presence of a phosphate buffer.
40. The immunogenic composition of claim 1 , wherein said composition comprises histidine.
41. The immunogenic composition of claim 30 , wherein the meningococcal conjugate antigen comprises a diphtheria toxoid carrier protein.
42. The immunogenic composition of claim 30 , wherein the meningococcal conjugate antigen comprises a CRM 197 carrier protein.
43. The immunogenic composition of claim 31 , wherein the meningococcal conjugate antigen comprises a diphtheria toxoid carrier protein.
44. The immunogenic composition of claim 31 , wherein the meningococcal conjugate antigen comprises a CRM 197 carrier protein.