Papilloma virus capsomere formulations and method of use

• US 6,228,368 B1
• Filed: 10/06/1997
• Issued: 05/08/2001
• Est. Priority Date: 10/06/1997
• Status: Expired due to Fees

• Current Assignee: Loyola University Chicago
• Original Assignee: Loyola University Chicago
• Inventors: Muller, Martin, Gissmann, Lutz
• Primary Examiner(s): SALIMI, ALI REZA
• Application Number:
  US08/944,368
• Time in Patent Office: 1,310 Days
• Field of Search: 424/186.1, 424/192.1, 424/204.1, 435/235.1, 435/69.1, 435/69.3, 435/320.1, 435/348, 536/23.72, 536/23.4
• US Class Current: 424/204.1
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2710/20022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/20023 Virus like particles [VLP]
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y10S 977/802 Virus-based particle
• CPC Class Codes: Y10S 977/917 Vaccine

Abstract

Vaccine formulations comprising viral capsomeres are disclosed along with methods for their production. Therapeutic and prophylactic methods of use for the vaccine formulations are also disclosed.

Claims

1. An antigenic formulation comprising a human papilloma virus capsomere, said capsomere comprising a fusion protein comprising a human papilloma virus L1 protein adjacent amino acid residues from a second protein, said L1 protein and said amino acids from said second protein positioned to inhibit virus-like particle formation, said formulation evoking an immune response which neutralizes human papilloma virus virions.

4. The antigenic formulation of any one of claims 1, 2, or 3 protein is encoded in the genome of a human papilloma virus selected from the group consisting of HPV6, HPV11, HPV16, HPV18, HPV33, HPV35, and HPV45.

5. The antigenic formulation of claim 4 wherein the papilloma virus is HPV16.

15. A method of treating an individual infected with an HPV virus comprising the step of administering to a patient in need thereof an amount of the antigenic formulation of claims 1, 2, 3, 5, 7, 8, 11, 13, or 14 effective to reduce the level of HPV infection.

16. A method for preventing papilloma virus infection comprising the step of administering to an individual susceptible thereto an amount of the antigenic formulation of claims 1, 2, 3, 5, 7, 8, 11, 13, or 14 effective to inhibit HPV infection.

2. An antigenic formulation comprising a human papilloma virus capsomere, said capsomere comprising a truncated human papilloma virus L1 protein having a deletion of one or more amino acid residues necessary for formation of a virus-like particle, said formulation evoking an immune response which neutralizes human papilloma virus virions.

3. The antigenic formulation of claim 2 wherein said capsomere comprises a fusion protein comprising a truncated human papilloma virus L1 protein adjacent amino acid residues from a second protein.

6. The antigenic formulation of any one of claims 2, 3, or 5 wherein carboxy terminal amino acid residues are deleted from the L1 protein.

7. The antigenic formulation of claim 6 wherein 1 to 34 carboxy terminal amino acid residues are deleted from the L1 protein.

8. The antigenic formulation of claim 7 wherein 34 carboxy terminal amino acid residues are deleted from the L1 protein.

9. The antigenic formulation of any one of claims 2, 3, or 5 wherein amino terminal amino acid residues are deleted from the L1 protein.

10. The antigenic formulation of any one of claims 2, 3, or 5 wherein internal amino acid residues are deleted from the L1 protein.

11. The antigenic formulation of claim 10 wherein the amino acid residues deleted from the L1 protein comprise a nuclear localization signal.

12. The antigenic formulation of claims 2 or 3 wherein the amino acids residues from the second protein are derived from an HPV protein.

13. The antigenic formulation of claim 12 wherein the HPV protein is an early HPV protein.

14. The antigenic formulation of claim 12 wherein the early HPV protein is selected from the group consisting of E1, E2, E3, E4, E5, E6, and E7.