Home LiteratureArticle Details
PMID: 10438842 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen.

Journal of virology ·Vol. 73 ·No. 9 ·1999-09-00 ·Pages 7524-32

Hanke T, Samuel RV, Blanchard TJ, Neumann VC, Allen TM, Boyson JE, Sharpe SA, Cook N, Smith GL, Watkins DI, Cranage MP, McMichael AJ

Abstract

DNA and modified vaccinia virus Ankara (MVA) are vaccine vehicles suitable and safe for use in humans. Here, by using a multicytotoxic T-lymphocyte (CTL) epitope gene and a DNA prime-MVA boost vaccination regimen, high levels of CTLs specific for a single simian immunodeficiency virus (SIV) gag-derived epitope were elicited in rhesus macaques. These vaccine-induced CTLs were capable of killing SIV-infected cells in vitro. Fluorescence-activated cell sorter analysis using soluble tetrameric major histocompatibility complex-peptide complexes showed that the vaccinated animals had 1 to 5% circulating CD8(+) lymphocytes specific for the vaccine epitope, frequencies comparable to those in SIV-infected monkeys. Upon intrarectal challenge with pathogenic SIVmac251, no evidence for protection was observed in at least two of the three vaccinated animals. This study does not attempt to define correlates of protective immunity nor design a protective vaccine against immunodeficiency viruses, but it demonstrates clearly that the DNA prime-MVA boost regimen is an effective protocol for induction of CTLs in macaques. It also shows that powerful tools for studying the role of CTLs in the control of SIV and human immunodeficiency virus infections are now available: epitope-based vaccines, a protocol for an effective induction of CTLs in primates, and a simple and sensitive method for quantitation of epitope-specific T cells. The advantages of the DNA prime-MVA boost regimen as well as the correlations of tetramer staining of peripheral blood lymphocytes with CTL killing in vitro and postchallenge control of viremia are discussed.

MeSH Terms
Animals CD8-Positive T-Lymphocytes Chick Embryo DNA, Viral/immunology Epitopes, T-Lymphocyte/immunology Genes, Viral Humans Macaca mulatta Mice Simian Immunodeficiency Virus/immunology T-Lymphocytes, Cytotoxic/immunology Vaccination Vaccines, DNA/immunology Vaccinia virus/genetics,immunology Viral Vaccines/immunology
Chemicals
DNA, Viral Epitopes, T-Lymphocyte Vaccines, DNA Viral Vaccines
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hanke T
Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom. [email protected]
Samuel R V
Blanchard T J
Neumann V C
Allen T M
Boyson J E
Sharpe S A
Cook N
Smith G L
Watkins D I
Cranage M P
McMichael A J
References (72)
72 references, click to expand
  1. Quantification of antigen specific CD8+ T cells using an ELISPOT assay.
    J Immunol Methods. 1995 Apr 12;181(1):45-54 PMID: 7537312
  2. ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids.
    J Clin Invest. 1995 Aug;96(2):867-76 PMID: 7635981
  3. High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors.
    J Virol. 1995 Sep;69(9):5838-42 PMID: 7637030
  4. E. coli beta-glucuronidase (GUS) as a marker for recombinant vaccinia viruses.
    Biotechniques. 1995 Sep;19(3):352-4, 356 PMID: 7495543
  5. Immunogenicity of the yeast recombinant p17/p24:Ty virus-like particles (p24-VLP) in healthy volunteers.
    Vaccine. 1995 Jun;13(9):831-4 PMID: 7483805
  6. HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women.
    Nat Med. 1995 Jan;1(1):59-64 PMID: 7584954
  7. Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques.
    Nat Med. 1995 Nov;1(11):1167-73 PMID: 7584989
  8. Immune responses in HIV-exposed seronegatives: have they repelled the virus?
    Curr Opin Immunol. 1995 Aug;7(4):448-55 PMID: 7495507
  9. Protective immunity does not correlate with the hierarchy of virus-specific cytotoxic T cell responses to naturally processed peptides.
    J Exp Med. 1998 May 18;187(10):1647-57 PMID: 9584143
  10. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine.
    J Gen Virol. 1998 May;79 ( Pt 5):1159-67 PMID: 9603331
  11. Viral immune evasion due to persistence of activated T cells without effector function.
    J Exp Med. 1998 Dec 21;188(12):2205-13 PMID: 9858507
  12. Dynamics of macrophage and T cell infection by HIV.
    J Theor Biol. 1999 Jan 7;196(1):101-13 PMID: 9892559
  13. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.
    Science. 1999 Feb 5;283(5403):857-60 PMID: 9933172
  14. Effective induction of HIV-specific CTL by multi-epitope using gene gun in a combined vaccination regime.
    Vaccine. 1999 Feb 12;17(6):589-96 PMID: 10075166
  15. HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers.
    AIDS. 1999 Jan 14;13(1):23-9 PMID: 10207541
  16. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations.
    Nat Med. 1999 May;5(5):526-34 PMID: 10229229
  17. HIV-specific cytotoxic T lymphocytes in seropositive individuals.
    Nature. 1987 Jul 23-29;328(6128):345-8 PMID: 3496541
  18. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160.
    Nature. 1990 Jun 14;345(6276):622-5 PMID: 2190095
  19. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice.
    Vaccine. 1998 Feb;16(4):426-35 PMID: 9607066
  20. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell.
    Nature. 1998 Jun 4;393(6684):474-8 PMID: 9624003
  21. Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
    Nature. 1998 Jun 4;393(6684):478-80 PMID: 9624004
  22. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions.
    Nature. 1998 Jun 4;393(6684):480-3 PMID: 9624005
  23. Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus.
    J Immunol. 1998 Jun 15;160(12):6062-71 PMID: 9637523
  24. Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10112-6 PMID: 9707609
  25. In vivo resistance to simian immunodeficiency virus superinfection depends on attenuated virus dose.
    J Gen Virol. 1998 Aug;79 ( Pt 8):1935-44 PMID: 9714241
  26. Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization.
    J Exp Med. 1998 Sep 21;188(6):1075-82 PMID: 9743526
  27. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.
    J Clin Invest. 1998 Nov 1;102(9):1758-65 PMID: 9802890
  28. A protective cytotoxic T cell response to a subdominant epitope is influenced by the stability of the MHC class I/peptide complex and the overall spectrum of viral peptides generated within infected cells.
    Eur J Immunol. 1998 Oct;28(10):3301-11 PMID: 9808199
  29. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus.
    J Virol. 1998 Dec;72(12):10180-8 PMID: 9811759
  30. A pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency virus-infected macaques.
    J Virol. 1998 Dec;72(12):10281-5 PMID: 9811776
  31. The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses.
    J Exp Med. 1998 Dec 21;188(12):2199-204 PMID: 9858506
  32. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542-6 PMID: 1988952
  33. Definition of an epitope and MHC class I molecule recognized by gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys.
    J Immunol. 1991 Jul 1;147(1):320-9 PMID: 1711081
  34. Cytotoxic T-cell response to simian immunodeficiency virus by cynomolgus macaque monkeys immunized with recombinant vaccinia virus.
    AIDS. 1991 Mar;5(3):317-20 PMID: 2059372
  35. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody.
    Nature. 1992 Feb 20;355(6362):728-30 PMID: 1741059
  36. Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1.
    J Infect Dis. 1992 Jun;165(6):1012-9 PMID: 1533867
  37. Cytotoxic T lymphocytes do not appear to select for mutations in an immunodominant epitope of simian immunodeficiency virus gag.
    J Immunol. 1992 Dec 15;149(12):4060-6 PMID: 1460291
  38. Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease.
    J Exp Med. 1993 Feb 1;177(2):249-56 PMID: 8093890
  39. HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant.
    Lancet. 1993 Apr 3;341(8849):860-1 PMID: 8096564
  40. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1.
    N Engl J Med. 1996 May 9;334(19):1222-30 PMID: 8606717
  41. Induction of bystander T cell proliferation by viruses and type I interferon in vivo.
    Science. 1996 Jun 28;272(5270):1947-50 PMID: 8658169
  42. Phenotypic analysis of antigen-specific T lymphocytes.
    Science. 1996 Oct 4;274(5284):94-6 PMID: 8810254
  43. 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
  44. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.
    Nat Med. 1997 Feb;3(2):212-7 PMID: 9018241
  45. Rhesus macaques previously infected with simian/human immunodeficiency virus are protected from vaginal challenge with pathogenic SIVmac239.
    J Virol. 1997 Mar;71(3):1911-21 PMID: 9032322
  46. Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms.
    J Virol. 1997 Apr;71(4):3120-8 PMID: 9060675
  47. Increased in vitro tetanus-induced production of HIV type 1 following in vivo immunization of HIV type 1-infected individuals with tetanus toxoid.
    AIDS Res Hum Retroviruses. 1997 Apr 10;13(6):473-80 PMID: 9100988
  48. Long-term non-progressive human immunodeficiency virus infection: new insights from the simian immunodeficiency virus model.
    J Gen Virol. 1997 May;78 ( Pt 5):979-84 PMID: 9152413
  49. Protection of monkeys vaccinated with vpr- and/or nef-defective simian immunodeficiency virus strain mac/human immunodeficiency virus type 1 chimeric viruses: a potential candidate live-attenuated human AIDS vaccine.
    J Gen Virol. 1997 May;78 ( Pt 5):985-9 PMID: 9152414
  50. Enhancement of immunodeficiency virus-specific immune responses in DNA-immunized rhesus macaques.
    Vaccine. 1997 Jun;15(8):924-6 PMID: 9234549
  51. Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4(+) T cells from exposed uninfected individuals expressing the wild-type CCR-5 allele.
    J Exp Med. 1997 Aug 4;186(3):455-60 PMID: 9236198
  52. Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination.
    Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9378-83 PMID: 9256490
  53. Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection.
    J Virol. 1997 Oct;71(10):7518-25 PMID: 9311831
  54. Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV.
    Immunol Cell Biol. 1997 Aug;75(4):389-96 PMID: 9315483
  55. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.
    Science. 1997 Nov 21;278(5342):1447-50 PMID: 9367954
  56. A high frequency of Mamu-A*01 in the rhesus macaque detected by polymerase chain reaction with sequence-specific primers and direct sequencing.
    Tissue Antigens. 1997 Dec;50(6):657-61 PMID: 9458122
  57. Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.
    J Gen Virol. 1998 Jan;79 ( Pt 1):83-90 PMID: 9460927
  58. Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime.
    Vaccine. 1998 Mar;16(5):439-45 PMID: 9491498
  59. Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans.
    Nature. 1998 Feb 26;391(6670):908-11 PMID: 9495345
  60. Dendritic cells and the control of immunity.
    Nature. 1998 Mar 19;392(6673):245-52 PMID: 9521319
  61. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.
    Science. 1998 Mar 27;279(5359):2103-6 PMID: 9516110
  62. Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes.
    Curr Biol. 1998 Mar 12;8(6):355-8 PMID: 9512422
  63. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara.
    Nat Med. 1998 Apr;4(4):397-402 PMID: 9546783
  64. Analysis of Gag-specific cytotoxic T lymphocytes in simian immunodeficiency virus-infected rhesus monkeys by cell staining with a tetrameric major histocompatibility complex class I-peptide complex.
    J Exp Med. 1998 May 4;187(9):1373-81 PMID: 9565630
  65. HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood.
    JAMA. 1994 Jan 5;271(1):42-6 PMID: 8258885
  66. 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
  67. 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
  68. A simian immunodeficiency virus envelope V3 cytotoxic T-lymphocyte epitope in rhesus monkeys and its restricting major histocompatibility complex class I molecule Mamu-A*02.
    J Virol. 1994 Oct;68(10):6690-6 PMID: 7521921
  69. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes.
    J Immunol. 1994 Dec 15;153(12):5586-92 PMID: 7527444
  70. A MHC class I B locus allele-restricted simian immunodeficiency virus envelope CTL epitope in rhesus monkeys.
    J Immunol. 1995 Mar 1;154(5):2516-22 PMID: 7532670
  71. A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge.
    J Virol. 1995 Apr;69(4):2279-84 PMID: 7884874
  72. Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics.
    J Exp Med. 1995 Apr 1;181(4):1365-72 PMID: 7699324
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.9.7524-7532.1999
Email
[email protected]
Published
1999-09-00
Pages
7524-32
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC104279
Subset
IM
Grants
NCRR NIH HHS · P51 RR000167 · United States
NIAID NIH HHS · AI32426 · United States
NIAID NIH HHS · AI41913 · United States
NCRR NIH HHS · RR00167 · United States
External Links
PubMed source DOI: 10.1128/JVI.73.9.7524-7532.1999 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2