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PMID: 17535971 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Intramural

Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses.

The Journal of experimental medicine ·Vol. 204 ·No. 6 ·2007-06-11 ·Pages 1405-16

Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Ambrozak DR, Asher TE, Douek DC, Harari A, Pantaleo G, Bailer R, Graham BS, Roederer M, Koup RA

Abstract

Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8(+) T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus-specific CD8(+) T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon gamma, interleukin 2, macrophage inflammatory protein 1beta, and tumor necrosis factor alpha after antigenic stimulation. Responding CD8(+) T cells exhibited an unusual phenotype (CD45RO(-)CD27(intermediate)). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8(+) T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated.

MeSH Terms
Adult Amino Acid Sequence CD8-Positive T-Lymphocytes/cytology,immunology Cytokines/metabolism Flow Cytometry Humans Immunization Immunophenotyping Molecular Sequence Data Smallpox Vaccine/immunology Vaccinia virus/immunology
Chemicals
Cytokines DryVax vaccine Smallpox Vaccine
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Precopio Melissa L
Immunology Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Betts Michael R
Parrino Janie
Price David A
Gostick Emma
Ambrozak David R
Asher Tedi E
Douek Daniel C
Harari Alexandre
Pantaleo Giuseppe
Bailer Robert
Graham Barney S
Roederer Mario
Koup Richard A
References (49)
49 references, click to expand
  1. Duration of antiviral immunity after smallpox vaccination.
    Nat Med. 2003 Sep;9(9):1131-7 PMID: 12925846
  2. Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype.
    J Virol. 2000 Oct;74(19):9144-51 PMID: 10982361
  3. Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox.
    Nature. 2004 Mar 11;428(6979):182-5 PMID: 15014500
  4. Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.
    J Exp Med. 2004 Jun 7;199(11):1585-93 PMID: 15184506
  5. Seventeen-colour flow cytometry: unravelling the immune system.
    Nat Rev Immunol. 2004 Aug;4(8):648-55 PMID: 15286731
  6. Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination.
    J Infect Dis. 2004 Oct 1;190(7):1286-94 PMID: 15346340
  7. Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence.
    J Gen Virol. 1991 May;72 ( Pt 5):1031-8 PMID: 2033387
  8. NYVAC: a highly attenuated strain of vaccinia virus.
    Virology. 1992 May;188(1):217-32 PMID: 1566575
  9. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.
    J Virol. 1994 Jul;68(7):4650-5 PMID: 8207839
  10. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection.
    J Virol. 1994 Sep;68(9):6103-10 PMID: 8057491
  11. Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation.
    J Immunol. 1995 Mar 15;154(6):2612-23 PMID: 7876536
  12. Principles for adoptive T cell therapy of human viral diseases.
    Annu Rev Immunol. 1995;13:545-86 PMID: 7612234
  13. Human cytotoxic T-cell memory: long-lived responses to vaccinia virus.
    J Virol. 1996 Apr;70(4):2627-31 PMID: 8642697
  14. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus.
    Nat Med. 1997 Feb;3(2):205-11 PMID: 9018240
  15. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.
    Nat Med. 1997 Feb;3(2):212-7 PMID: 9018241
  16. Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection.
    Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1890-5 PMID: 9050875
  17. Phenotypic and functional separation of memory and effector human CD8+ T cells.
    J Exp Med. 1997 Nov 3;186(9):1407-18 PMID: 9348298
  18. Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia.
    Nature. 2000 Sep 21;407(6802):386-90 PMID: 11014195
  19. A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape.
    J Immunol. 2002 Mar 15;168(6):3099-104 PMID: 11884484
  20. Recombinant vaccinia virus-induced T-cell immunity: quantitation of the response to the virus vector and the foreign epitope.
    J Virol. 2002 Apr;76(7):3329-37 PMID: 11884558
  21. Epitope-specific evolution of human CD8(+) T cell responses from primary to persistent phases of Epstein-Barr virus infection.
    J Exp Med. 2002 Apr 1;195(7):893-905 PMID: 11927633
  22. Phenotypic and functional heterogeneity of EBV epitope-specific CD8+ T cells.
    J Immunol. 2002 Apr 15;168(8):4184-91 PMID: 11937579
  23. Dose-related effects of smallpox vaccine.
    N Engl J Med. 2002 Apr 25;346(17):1275-80 PMID: 11923489
  24. Ex vivo detection and enumeration of human antigen-specific CD8+ T lymphocytes using antigen delivery by a recombinant vaccinia expression vector and intracellular cytokine staining.
    J Immunol Methods. 2002 Apr 1;262(1-2):167-80 PMID: 11983230
  25. Identification of naive or antigen-experienced human CD8(+) T cells by expression of costimulation and chemokine receptors: analysis of the human cytomegalovirus-specific CD8(+) T cell response.
    J Immunol. 2002 Jun 1;168(11):5455-64 PMID: 12023339
  26. Primary induction of human CD8+ cytotoxic T lymphocytes and interferon-gamma-producing T cells after smallpox vaccination.
    J Infect Dis. 2002 Jun 1;185(11):1657-9 PMID: 12023773
  27. Novel CD8+ T cell antagonists based on beta 2-microglobulin.
    J Biol Chem. 2002 Jun 7;277(23):20840-6 PMID: 11914379
  28. IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains.
    Dev Comp Immunol. 2003 Jan;27(1):55-77 PMID: 12477501
  29. CD45: a critical regulator of signaling thresholds in immune cells.
    Annu Rev Immunol. 2003;21:107-37 PMID: 12414720
  30. Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.
    J Exp Med. 2003 Apr 7;197(7):927-32 PMID: 12668642
  31. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans.
    Nat Med. 2003 Jun;9(6):729-35 PMID: 12766765
  32. Host range and cytopathogenicity of the highly attenuated MVA strain of vaccinia virus: propagation and generation of recombinant viruses in a nonhuman mammalian cell line.
    Virology. 1997 Nov 24;238(2):198-211 PMID: 9400593
  33. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.
    Science. 1999 Feb 5;283(5403):857-60 PMID: 9933172
  34. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques.
    J Exp Med. 1999 Mar 15;189(6):991-8 PMID: 10075982
  35. Cytotoxic T lymphocytes, chemokines and antiviral immunity.
    Immunol Today. 1999 May;20(5):212-6 PMID: 10322299
  36. Human virus-specific CD8+ CTL clones revert from CD45ROhigh to CD45RAhigh in vivo: CD45RAhighCD8+ T cells comprise both naive and memory cells.
    J Immunol. 1999 Jun 15;162(12):7080-7 PMID: 10358151
  37. HIV-1-specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells.
    Proc Natl Acad Sci U S A. 2005 May 17;102(20):7239-44 PMID: 15872023
  38. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus.
    Nat Med. 2005 Jul;11(7):740-7 PMID: 15951823
  39. HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation.
    Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13980-5 PMID: 16172378
  40. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses.
    J Exp Med. 2005 Nov 21;202(10):1349-61 PMID: 16287711
  41. Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara.
    J Immunol. 2005 Dec 15;175(12):8431-7 PMID: 16339586
  42. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells.
    Blood. 2006 Jun 15;107(12):4781-9 PMID: 16467198
  43. Amine reactive dyes: an effective tool to discriminate live and dead cells in polychromatic flow cytometry.
    J Immunol Methods. 2006 Jun 30;313(1-2):199-208 PMID: 16756987
  44. Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry.
    Nat Med. 2006 Aug;12(8):972-7 PMID: 16862156
  45. Safety, immunogenicity and efficacy of modified vaccinia Ankara (MVA) against Dryvax challenge in vaccinia-naïve and vaccinia-immune individuals.
    Vaccine. 2007 Feb 9;25(8):1513-25 PMID: 17126963
  46. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major.
    Nat Med. 2007 Jul;13(7):843-50 PMID: 17558415
  47. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.
    Nature. 1999 Oct 14;401(6754):708-12 PMID: 10537110
  48. Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef.
    Nat Med. 1999 Nov;5(11):1270-6 PMID: 10545993
  49. Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation.
    J Immunol Methods. 2003 Oct 1;281(1-2):65-78 PMID: 14580882
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20062363
Published
2007-06-11
Epub
2007-00-29
Pages
1405-16
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118607
Subset
IM
Grants
Medical Research Council · G0501963 · United Kingdom
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1084/jem.20062363 PMC Full Text View journal details
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