Stabilizers containing recombinant human serum albumin for live virus vaccines

• US 6,210,683 B1
• Filed: 08/26/1998
• Issued: 04/03/2001
• Est. Priority Date: 09/05/1997
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Volkin, David, Burke, Carl
• Primary Examiner(s): Wortman, Donna C.
• Application Number:
  US09/140,428
• Time in Patent Office: 951 Days
• Field of Search: 424/218.1, 424/230.1, 424/212.1, 424/219.1, 435/237, 435/239
• US Class Current: 424/230.1
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/0015 Combination vaccines based on measles-mumps-rubella
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/165 Mumps or measles virus
• CPC Class Codes: A61K 39/20 Rubella virus
• CPC Class Codes: A61K 39/25 Varicella-zoster virus
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: C12N 2710/16734 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compositions are provided for improving the stability of live virus vaccines containing, e.g., live varicella zoster, measles, mumps, and rubella viruses. Such improved stabilizers are aqueous solutions containing recombinant human serum albumin (rHA) as a component at from 1-100 g/l. Live virus vaccines as well as methods of preparing live virus vaccines containing the stabilizers are also provided.

Claims

1. A live virus vaccine comprising:

(a) live varicella zoster; and

(b) recombinant human serum albumin (rHA) at a concentration of 0.1% to 10% (w/v) wherein the rHA has been made in yeast.

2. A live virus vaccine prepared by lyophilizing the vaccine of claim 1.

3. The vaccine of claim 2 wherein the yeast is Saccharomyces cerevisiae.

4. The vaccine of claim 1 wherein the rHA concentration is from 0.5% to 5%.

5. The vaccine of claim 1 wherein the rHA concentration is from 1% to 3%.

6. The vaccine of claim 1 further comprising measles, mumps, and rubella viruses.

7. The vaccine of claim 1 further comprising a sugar or sugar alcohol at 20-90 g/l;

a mono- or dibasic alkali metal phosphate salt or mixture thereof at a total phosphate concentration of from 0.5 to 3 g/l;

a glutamic acid alkali metal salt at 0.5 to 2 g/l; and

a combination of sodium and potassium chloride providing a total chloride concentration of 4-10 g/l.

8. The vaccine of claim 1 further comprising, per liter:

9. The vaccine of claim 8 comprising, per liter:

10. The vaccine of claim 1 further comprising, per liter:

sorbitol at 20-90 g/l;

sucrose at 0-70 g/l;

1 M Sodium Phosphate, pH 6.2, at 65-85 mL; and

Tissue Culture Medium.

11. The vaccine of claim 1 wherein the rHA concentration is 26.75 g/l and further comprising, per liter:

12. The vaccine of claim 1 wherein the rHA concentration is 39.75 g/l and further comprising, per liter:

13. The vaccine of claim 1 wherein the yeast is Saccharomyces cerevisiae.

14. A live virus vaccine comprising:

(a) live varicella zoster; and

(b) Medium 199 containing;

rHA at a concentration of 0.1% to 10%;

50 μ

g/ml neomycin;

2 mM L-glutamine and;

25% SPG

where SPG contains, on a per liter basis;

15. A method of preparing a live virus vaccine that comprises mixing live varicella zoster with a stabilizer comprising an aqueous solution of recombinant human serum albumin (rHA) at 1-100 g/l;

a sugar or sugar alcohol at 20-90 g/l;

a mono- or dibasic alkali metal phosphate salt or mixture thereof at a total phosphate concentration of from 0.5 to 3 g/l;

a glutamic acid alkali metal salt at 0.5 to 2 g/l; and

a combination of sodium and potassium chloride providing a total chloride concentration of 4-10 g/l wherein the rHA has been made in yeast.

16. The method of claim 15 wherein the ratio of live virus preparation to stabilizer is between 1:

100 and 1;

1 (v/v).

17. The method of claim 16 wherein the ratio of live virus preparation to stabilizer is 1:

3 (v/v).

18. The method of claim 16 wherein the ratio of live virus preparation to stabilizer is 1:

2 (v/v).

19. A method of harvesting varicella zoster virus for use in a live virus vaccine that includes the step of disrupting cells containing varicella zoster virus in the presence of a stabilizer comprising an aqueous solution of recombinant human serum albumin (rHA) at 1-100 g/l;

a sugar or sugar alcohol at 20-90 g/l;

a mono- or dibasic alkali metal phosphate salt or mixture thereof at a total phosphate concentration of from 0.5 to 3 g/l;

a glutamic acid alkali metal salt at 0.5 to 2 g/l; and

a combination of sodium and potassium chloride providing a total chloride concentration of 4-10 g/l wherein the rHA has been made in yeast.