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Infection and Immunity, February 2001, p. 681-686, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.681-686.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Enhanced Immunogenicity of CD4+ T-Cell Responses and Protective Efficacy of a DNA-Modified Vaccinia Virus Ankara Prime-Boost Vaccination Regimen for Murine Tuberculosis

Helen McShane,1,2,* Roger Brookes,1 Sarah C. Gilbert,2 and Adrian V. S. Hill1,2

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU,1 and Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN,2 United Kingdom

Received 21 July 2000/Returned for modification 25 September 2000/Accepted 28 October 2000

DNA vaccines whose DNA encodes a variety of antigens from Mycobacterium tuberculosis have been evaluated for immunogenicity and protective efficacy. CD8+ T-cell responses and protection achieved in other infectious disease models have been optimized by using a DNA immunization to prime the immune system and a recombinant virus encoding the same antigen(s) to boost the response. A DNA vaccine (D) and recombinant modified vaccinia virus Ankara (M) in which the DNA encodes early secreted antigenic target 6 and mycobacterial protein tuberculosis 63 synthesized, and each was found to generate specific gamma interferon (IFN-gamma )-secreting CD4+ T cells. Enhanced CD4+ IFN-gamma T-cell responses were produced by both D-M and M-D immunization regimens. Significantly higher levels of IFN-gamma were seen with a D-D-D-M immunization regimen. The most immunogenic regimens were assessed in a challenge study and found to produce protection equivalent to that produced by Mycobacterium bovis BCG. Thus, heterologous prime-boost regimens boost CD4+ as well as CD8+ T-cell responses, and the use of heterologous constructs encoding the same antigen(s) may improve the immunogenicity and protective efficacy of DNA vaccines against tuberculosis and other diseases.

* Corresponding author. Mailing address: Level 7/Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU. Phone: 01865 221609. Fax: 01865 221921. E-mail: helen.mcshane{at}ndm.ox.ac.uk.

Infection and Immunity, February 2001, p. 681-686, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.681-686.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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