Polyinosinic acid-polycytidylic acid-based adjuvant
The present invention provides a polynucleotide adjuvant composition and methods of use in eliciting an immune response. The present invention also provides an immunogenic composition comprising the polynucleotide adjuvant composition together with an antigen (e.g., as in a vaccine). The adjuvant compositions of the invention have particular physical properties (e.g., molecular weight, concentration, and pH) which address the need for a safe adjuvant for eliciting an enhanced immune response. The present invention further contemplates methods of use of such adjuvant compositions, particularly in eliciting an immune response to an antigenic compound.
1. A polynucleotide adjuvant composition comprising:
a polyriboinosinic-polyribocytidylic acid (PIC),
an antibiotic, and
a positive ion,
wherein the composition is suitable for use in humans and contains polynucleotide adjuvant composition molecules heterogeneous for at least one of molecular weight or size, wherein the molecular weight is in a molecular weight range of from 338,000 to 1,200,000 Daltons and wherein the size is in a molecular size range of from 13.5 to 24.0 Svedbergs.
2. A polynucleotide adjuvant composition comprising:
a polyriboinosinic-polyribocytidylic acid (PIC),
an antibiotic, and
a positive ion,
wherein the composition is suitable for use in humans and contains polynucleotide adjuvant composition molecules that have an average molecular weight greater than 338,000 Daltons or have an average molecular size greater than 13.5 Svedbergs.
3. The polynucleotide adjuvant composition of claim 2 , wherein the average molecular weight is equal to or greater than 500,000 Daltons or the average molecular size is equal to or greater than 15 Svedbergs.
4. The polynucleotide adjuvant composition of any of claims 1 , 2 or 3 , wherein the antibiotic is kanamycin, neomycin, an anthracycline, butirosin sulfate, a gentamicin, hygromycin, amikacin, dibekacin, nebramycin, metrzamide, puromycin, streptomycin, or streptozocin.
5. The polynucleotide adjuvant composition of any of claims 1 , 2 or 3 , wherein the antibiotic is kanamycin, neomycin, an anthracycline, butirosin sulfate, a gentamicin, hygromycin, amikacin, dibekacin, nebramycin, metrzamide, puromycin, streptomycin, or streptozocin and the positive ion is calcium, cadmium, lithium, magnesium, cerium, cesium, chromium, cobalt, deuterium, gallium, iodine, iron, or zinc; and wherein the positive ion is the form of an inorganic salt or an organic complex.
6. The polynucleotide adjuvant composition of any of claims 1 , 2 or 3 , wherein the antibiotic is kanamycin, neomycin, an anthracycline, butirosin sulfate, a gentamicin, hygromycin, amikacin, dibekacin, nebramycin, metrzamide, puromycin, streptomycin, or streptozocin and the source of positive ions is calcium chloride, calcium carbonate, calcium fluoride, calcium hydroxide, calcium phosphates, or calcium sulfate.
7. The polynucleotide adjuvant composition of any of claims 1 , 2 or 3 , wherein the antibiotic is kanamycin sulfate and the positive ion is provided by calcium chloride.
8. A kit comprising the polynucleotide adjuvant composition of any of claims 1 , 2 or 3 and an antigenic compound, wherein the antibiotic is kanamycin sulfate and the positive ion is provided by calcium chloride.
9. A method for enhancing an immune response to an antigenic compound, comprising: administering to a subject a composition comprising an antigenic compound and the polynucleotide adjuvant composition of any of claims 1 , 2 or 3 , wherein the antibiotic is kanamycin sulfate and the positive ion is provided by calcium chloride.
10. The method of claim 9 , wherein said administering is by parenteral injection, intramuscular injection, intraperitoneal injection, intravenous injection, subcutaneous injection, inhalation, rectal delivery, vaginal delivery, nasal delivery, oral delivery, opthamalic delivery, topical delivery, transdermal delivery or intradermal delivery.
11. The polynucleotide adjuvant composition of claim 4 , wherein the antibiotic is kanamycin.
12. The polynucleotide adjuvant composition of any of claims 1 , 2 or 3 , wherein the positive ion is calcium, cadmium, lithium, magnesium, cerium, cesium, chromium, cobalt, deuterium, gallium, iodine, iron, or zinc.
13. The polynucleotide adjuvant composition of claim 12 , wherein the positive ion is calcium.
14. An immunogenic composition, comprising:
a polynucleotide adjuvant composition comprising a polyriboinosinic-polyribocytidylic acid (PIC), an antibiotic, and a positive ion; and
an antigenic compound;
wherein the composition is suitable for use in humans and contains polynucleotide adjuvant composition molecules that have an average molecular weight greater than 338,000 Daltons or have an average molecular size greater than 13.5 Svedbergs.
15. The immunogenic composition of claim 14 , wherein the antibiotic is kanamycin sulfate and the positive ion is provided by calcium chloride.
16. The immunogenic composition of claim 14 , wherein the antigenic compound is a human antigen, a non-human animal antigen, a plant antigen, bacterial antigen, a fungal antigen, a viral antigen, a parasite antigen, or a cancer antigen.
17. The immunogenic composition of claim 16 , wherein the viral antigen is a rabies antigen.
18. The immunogenic composition of claim 17 , wherein the rabies antigen is an inactivated purified rabies antigen.
19. The immunogenic composition of claim 14 , wherein polynucleotide adjuvant composition is capable of eliciting an enhanced specific humoral and/or cell mediated immune response.
20. The immunogenic composition of claim 14 , wherein at least one of the adjuvant composition or the immunogenic composition is in a solid form or a liquid form, wherein the liquid form is a solution or a suspension.
21. The immunogenic composition of claim 14 , wherein at least one of the adjuvant composition or the immunogenic composition is freeze-dried.
22. An immunogenic composition, comprising:
a polynucleotide adjuvant composition comprising a polyriboinosinic-polyribocytidylic acid (PIC), an antibiotic, and a positive ion, wherein the antibiotic is kanamycin and the positive ion is calcium; and
an antigenic compound;
wherein the composition is suitable for use in humans and contains polynucleotide adjuvant composition molecules that have an average molecular weight greater than 338,000 Daltons or have an average molecular size greater than 13.5 Svedbergs.
23. The immunogenic composition of claim 22 , wherein the antigenic compound is a human antigen, a non-human animal antigen, a plant antigen, bacterial antigen, a fungal antigen, a viral antigen, a parasite antigen, or a cancer antigen.
24. The immunogenic composition of claim 23 , wherein the viral antigen is a rabies antigen.
25. The immunogenic composition of claim 24 , wherein the rabies antigen is an inactivated purified rabies antigen.
26. The immunogenic composition of claim 22 , wherein polynucleotide adjuvant composition is capable of eliciting an enhanced specific humoral and/or cell mediated immune response.
27. The immunogenic composition of claim 22 , wherein at least one of the adjuvant composition or the immunogenic composition is in a solid form or a liquid form, wherein the liquid form is a solution or a suspension.
28. The immunogenic composition of claim 22 , wherein at least one of the adjuvant composition or the immunogenic composition is freeze-dried.
29. An immunogenic composition, comprising:
a polynucleotide adjuvant composition comprising a polyriboinosinic-polyribocytidylic acid (PIC), an antibiotic, and a positive ion; and
an antigenic compound;
wherein the composition is suitable for use in humans and contains polynucleotide adjuvant composition molecules heterogeneous for at least one of molecular weight or size, wherein the molecular weight is in a molecular weight range of from 338,000 to 1,200,000 Daltons and wherein the size is in a molecular size range of from 13.5 to 24.0 Svedberg.
30. The immunogenic composition of claim 29 , wherein the antibiotic is kanamycin sulfate and the positive ion is provided by calcium chloride.
31. The immunogenic composition of claim 29 , wherein the antigenic compound is a human antigen, a non-human animal antigen, a plant antigen, bacterial antigen, a fungal antigen, a viral antigen, a parasite antigen, or a cancer antigen.
32. The immunogenic composition of claim 31 , wherein the viral antigen is a rabies antigen.
33. The immunogenic composition of claim 32 , wherein the rabies antigen is an inactivated purified rabies antigen.
34. The immunogenic composition of claim 29 , wherein polynucleotide adjuvant composition is capable of eliciting an enhanced specific humoral and/or cell mediated immune response.
35. The immunogenic composition of claim 29 , wherein at least one of the adjuvant composition or the immunogenic composition is in a solid form or a liquid form, wherein the liquid form is a solution or a suspension.
36. The immunogenic composition of claim 29 , wherein at least one of the adjuvant composition or the immunogenic composition is freeze-dried.
37. A method for enhancing an immune response to an antigenic compound, comprising: administering to a subject the immunogenic composition of claims 14 , 22 or 29 , wherein the antibiotic is kanamycin sulfate and the positive ion is provided by calcium chloride.
38. The method of claim 37 , wherein said administering is by parenteral injection, intramuscular injection, intraperitoneal injection, intravenous injection, subcutaneous injection, inhalation, rectal delivery, vaginal delivery, nasal delivery, oral delivery, opthamalic delivery, topical delivery, transdermal delivery or intradermal delivery.