Accelerated CD8+ T-cell memory after dendritic cell vaccination

• US 20060204509A1
• Filed: 03/14/2006
• Published: 09/14/2006
• Est. Priority Date: 03/14/2005
• Status: Abandoned Application

• Current Assignee: University of Iowa Research Foundation
• Original Assignee: University of Iowa Research Foundation
• Inventors: Messingham, Kelly A.N., Badovinac, Vladimir P., Harty, John T.
• Application Number:
  US11/375,653
• Publication Number:
  US 20060204509A1
• Time in Patent Office: Days
• US Class Current: 424/184.100
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/464456 Tyrosinase or tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/4648 Bacterial antigens

Abstract

Disclosed are compositions and methods for Here, it is shown that vaccination with peptide-coated dendritic cells (DC) generated antigen-(Ag)-specific CD8⁺ T-cells with the phenotype and function of memory T-cells as early as 4-6 days after immunization. These memory-like CD8⁺ T-cells underwent vigorous secondary expansion, resulting in rapid generation of elevated secondary memory CD8+ T-cell numbers and increased protective immunity, in response to a variety of booster immunizations. However, concurrent inflammation prevented the rapid generation of memory T-cells by DC immunization. Thus, DC vaccination, in the absence of overt inflammation, accelerated memory cell generation and dramatically reduced the interval required for booster amplification of memory CD8⁺ T-cell numbers.

Claims

1. A method of producing memory T-cells specific for a target in a subject comprising administering to the subject a mixture comprising an antigen related to the target and a dendritic cell (DC), and administering a booster to the subject less than 6 months from initial antigen contact, and wherein the memory T-cells generated are able to proliferate upon encounter with the booster.

2. The method of claim 1, wherein the booster is administered less than 5 months, 4 months, 3 months, 2 months, 1 month, 4 weeks, 3 weeks, 2 weeks, 13 days, 12 days, 11 days, 10 days, 9 days, 8 days, 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, or 1 day after initial antigen contact.

3. The method of claim 1, wherein the dendritic cells originated from the subject to be vaccinated.

4. The method of claim 1, wherein the dendritic cell is a mature dendritic cell.

5. The method of claim 1, wherein the dendritic cell is a dendritic cell progenitor.

6. The method of claim 1, wherein the antigen is selected from the group of antigens consisting of a peptide, polypeptide, protein, heat-killed pathogen, live attenuated pathogen, or cancer.

7. The method of claim 1, wherein the antigen comprises more than 1 antigen.

8. The method of claim 7, wherein the antigens originate from the same pathogen.

9. The method of claim 7, wherein the antigens originate from heterologous pathogens.

10. The method of claim 1, wherein the antigen is expressed in a vector.

11. The method of claim 1, wherein the antigen is one component in a first vaccine.

12. The method of claim 1, wherein the subject is a mammal, human, mouse, pig, cow, horse, or chicken.

13. The method of claim 1, further comprising administering to the subject a second antigen.

14. The method of claim 13, wherein the first antigen and the second antigen are the same antigen.

15. The method of claim 13, wherein the second antigen is selected from the group of antigens consisting of a peptide, polypeptide, protein, heat-killed pathogen, live attenuated pathogen, or cancer.

16. The method of claim 13, wherein the second antigen is expressed in a vector.

17. The method of claim 13, wherein the second antigen is one component in a second vaccine.

18. The method of claim 13, wherein the second antigen is administered 6, 10, 14, 18, 21, 30, 60, 90, 120, or 180 days after the first antigen.

19. The method of claim 1, whereby the initial DC administration is followed within one week by a booster administration leading to 5-300-fold increases in the number of antigen-specific effector CD8⁺ T-cells within five days after booster administration.

20. The method of claim 19 where the booster administration leads to 3-30-fold increases in the number of memory CD8⁺ T-cells compared to DC vaccination alone and within 30 days after the initial administration.

21. A method of producing protective immunity to a target in a subject, comprising administering a mixture comprising an antigen related to the target and a dendritic cell, wherein the protective immunity is generated within one week, and wherein the subject has sought to achieve protective immunity in an accelerated way.

22. A method of generating a protective amount of central memory T-cells in a subject to multiple antigens comprising mixing dendritic cells with the antigens and administering the mixture to the subject, wherein the protective amount of central memory T-cells are generated more quickly than are generated with the antigen alone.

23. A method of making a vaccine to an antigen comprising mixing a dendritic cell with the antigen and administering the mixture to a subject, wherein the mixture increases the number of T-cells specific to the antigen in the subject.

24. A method of making a vaccine to an antigen comprising mixing dendritic cells with the antigen and administering the mixture to a subject, wherein the mixture accelerates the production of memory T-cells specific to the antigen in the subject.

25. The method of claim 24, wherein the mixture also accelerates the production of the number of effector cells.

26. A method of making a vaccine to an antigen comprising mixing dendritic cells with the antigen and administering the mixture to a subject, wherein the mixture accelerates the production of the effector and memory T-cells specific to the antigen in the subject.

27. A method of making a vaccine specific for a subject in need thereof comprising removing dendritic cells from the subject to be vaccinated, mixing an antigen with the dendritic cells, administering the mixture to the subject.

28. A composition comprising dendritic cells and one or more antigens, wherein the dendritic cells and antigen are in sufficient quantity to induce a protective immune response more quickly and with greater magnitude then antigen alone, wherein the dendritic cells comprise the common MHC alleles for a given population, and wherein the antigen comprise immunodominant peptides corresponding to the MHC alleles.

29. A method of accelerating the production of a protective amount of central memory T-cells in a subject to an antigen comprising mixing dendritic cells with the antigen and administering the mixture to the subject.

30. A method of accelerating the production of a protective amount of central memory T-cells in a subject to multiple antigens comprising mixing dendritic cells with the antigens and administering the mixture to the subject.

31. A method of making a vaccine to an antigen comprising mixing dendritic cells with the antigen and administering the mixture to a subject, wherein the mixture accelerates the transition from effector to memory T-cells specific to the antigen in the subject.