International Immunology, Vol. 14, No. 1, 31-37,
January 2002
© 2002 Japanese Society for Immunology
Prime–boost immunization generates a high frequency, high-avidity CD8+ cytotoxic T lymphocyte population
John Curtin School of Medical Research, Australian National University, Canberra, ACT 2610, Australia.
1 Gene Therapy Program, LSU/Tulane Gene Therapy Consortium, LSU Health Sciences Center, New Orleans, LA 70112, USA.
2 Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052, Australia.
Correspondence to: M. J. Estcourt
Development and expansion of high-avidity T cell populations may be important for the success of immunization strategies against HIV and other pathogens that have presented major problems for vaccine development. We have used tetrameric–MHC complexes ex vivo and lytic assays to show that `prime-boost' immunization with DNA vaccines and recombinant poxvirus vectors generates high frequencies of cytotoxic T lymphocytes (CTL) that recognize target cells expressing very low levels of specific antigen. These cells persist for at least 6 months at levels representing ~10% of the CD8+ T cell population. Using a novel in vivo assay, we also found that prime-boost immunized animals were capable of eliminating target cells expressing 10- to 100-fold less immunogenic peptide than mice given either vector alone. In addition, viral challenge led to rapid expansion of CTL effectors in prime-boost groups, to levels representing >30% of total CD8+ T cell numbers. Strategies that generate specific T cells of high avidity, optimizing early detection of infected cells, offer new hope for effective prophylaxis and immunotherapy.
Keywords: antigens, cytotoxic, DNA, immunologic memory, immunotherapy, T lymphocytes, vaccines
Transmitting editor: D. Tarlinton
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Wang, I. E. A. Flesch, and D. C. Tscharke Vaccinia Virus CD8+ T-Cell Dominance Hierarchies Cannot Be Altered by Prior Immunization with Individual Peptides J. Virol., September 1, 2009; 83(17): 9008 - 9012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Li, M. Zhang, C. Zhou, X. Zhao, N. Iijima, and F. R. Frankel Novel Vaccination Protocol with Two Live Mucosal Vectors Elicits Strong Cell-Mediated Immunity in the Vagina and Protects against Vaginal Virus Challenge J. Immunol., February 15, 2008; 180(4): 2504 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Hutchings, A. J. Birkett, A. C. Moore, and A. V. S. Hill Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge Infect. Immun., December 1, 2007; 75(12): 5819 - 5826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Belyakov, S. Kozlowski, M. Mage, J. D. Ahlers, L. F. Boyd, D. H. Margulies, and J. A. Berzofsky Role of {alpha}3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs Int. Immunol., December 1, 2007; 19(12): 1413 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hanke, A. J. McMichael, and L. Dorrell Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction J. Gen. Virol., January 1, 2007; 88(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. De Rose, C. J. Batten, M. Z. Smith, C. S. Fernandez, V. Peut, S. Thomson, I. A. Ramshaw, B. E. H. Coupar, D. B. Boyle, V. Venturi, et al. Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques J. Virol., January 1, 2007; 81(1): 292 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Liang, J. V. van den Hurk, L. A. Babiuk, and S. van Drunen Littel-van den Hurk Priming with DNA encoding E2 and boosting with E2 protein formulated with CpG oligodeoxynucleotides induces strong immune responses and protection from Bovine viral diarrhea virus in cattle. J. Gen. Virol., October 1, 2006; 87(Pt 10): 2971 - 2982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Someya, Y. Ami, T. Nakasone, Y. Izumi, K. Matsuo, S. Horibata, K.-Q. Xin, H. Yamamoto, K. Okuda, N. Yamamoto, et al. Induction of Positive Cellular and Humoral Immune Responses by a Prime-Boost Vaccine Encoded with Simian Immunodeficiency Virus gag/pol J. Immunol., February 1, 2006; 176(3): 1784 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Clark, J. C. Kenyon, N. W. Bartlett, D. C. Tscharke, and G. L. Smith Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy J. Gen. Virol., January 1, 2006; 87(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Larke, A. Murphy, C. Wirblich, D. Teoh, M. J. Estcourt, A. J. McMichael, P. Roy, and T. Hanke Induction of Human Immunodeficiency Virus Type 1-Specific T Cells by a Bluetongue Virus Tubule-Vectored Vaccine Prime-Recombinant Modified Virus Ankara Boost Regimen J. Virol., December 1, 2005; 79(23): 14822 - 14833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Gherardi and M. Esteban Recombinant poxviruses as mucosal vaccine vectors J. Gen. Virol., November 1, 2005; 86(11): 2925 - 2936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chea, C. J. Dale, R. De Rose, I. A. Ramshaw, and S. J. Kent Enhanced Cellular Immunity in Macaques following a Novel Peptide Immunotherapy J. Virol., March 15, 2005; 79(6): 3748 - 3757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Morello, M. Ye, S. Hung, L. A. Kelley, and D. H. Spector Systemic Priming-Boosting Immunization with a Trivalent Plasmid DNA and Inactivated Murine Cytomegalovirus (MCMV) Vaccine Provides Long-Term Protection against Viral Replication following Systemic or Mucosal MCMV Challenge J. Virol., January 1, 2005; 79(1): 159 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Facciabene, L. Aurisicchio, and N. La Monica Baculovirus Vectors Elicit Antigen-Specific Immune Responses in Mice J. Virol., August 15, 2004; 78(16): 8663 - 8672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. van Broekhoven, C. R. Parish, C. Demangel, W. J. Britton, and J. G. Altin Targeting Dendritic Cells with Antigen-Containing Liposomes: A Highly Effective Procedure for Induction of Antitumor Immunity and for Tumor Immunotherapy Cancer Res., June 15, 2004; 64(12): 4357 - 4365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wong, M. Lara-Tejero, A. Ploss, I. Leiner, and E. G. Pamer Rapid Development of T Cell Memory J. Immunol., June 15, 2004; 172(12): 7239 - 7245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Doria-Rose, C. Ohlen, P. Polacino, C. C. Pierce, M. T. Hensel, L. Kuller, T. Mulvania, D. Anderson, P. D. Greenberg, S.-L. Hu, et al. Multigene DNA Priming-Boosting Vaccines Protect Macaques from Acute CD4+-T-Cell Depletion after Simian-Human Immunodeficiency Virus SHIV89.6P Mucosal Challenge J. Virol., November 1, 2003; 77(21): 11563 - 11577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Woodberry, J. Gardner, S. L. Elliott, S. Leyrer, D. M. Purdie, P. Chaplin, and A. Suhrbier Prime Boost Vaccination Strategies: CD8 T Cell Numbers, Protection, and Th1 Bias J. Immunol., March 1, 2003; 170(5): 2599 - 2604. [Abstract] [Full Text] [PDF]
|
|