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Infection and Immunity, June 2000, p. 3090-3096, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Protection against Virulent Mycobacterium avium Infection following DNA Vaccination with the 35-Kilodalton Antigen Is Accompanied by Induction of Gamma Interferon-Secreting CD4+ T Cells

Ela Martin,1,2 Arun T. Kamath,1 James A. Triccas,1 and Warwick J. Britton1,3,*

Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales 2042,1 The Cooperative Research Centre for Vaccine Technology, The Queensland Institute of Medical Research, Brisbane Hospital, Queensland 4029,2 and Department of Medicine, University of Sydney, New South Wales 2006,3 Australia

Received 21 September 1999/Returned for modification 26 October 1999/Accepted 18 February 2000

Mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of M. avium infection is also increasing in the immunocompetent population. The antigen repertoire of M. avium varies from that of Mycobacterium tuberculosis, with the immunodominant 35-kDa protein being present in M. avium and Mycobacterium leprae but not in members of the M. tuberculosis complex. Here we show that a DNA vector encoding this M. avium 35-kDa antigen (DNA-35) induces protective immunity against virulent M. avium infection, and this protective effect persists over 14 weeks of infection. In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a cytoplasmic or secreted protein, both induced strong T-cell gamma interferon (IFN-gamma ) and humoral immune responses. Furthermore, the antibody response was to conformational determinants, confirming that the vector-encoded protein had adopted the native conformation. DNA-35 immunization resulted in an increased activated/memory CD4+ T-cell response, with an accumulation of CD4+ CD44hi CD45RBlo T cells and an increase in antigen-specific IFN-gamma production. The protective effect of the DNA-35 vectors against M. avium infection was comparable to that of vaccination with Mycobacterium bovis BCG and significantly greater than that for previous treated infection with M. avium. These results illustrate the importance of the 35-kDa protein in the protective response to M. avium infection and indicate that DNA vaccination successfully promotes a sustained level of protection during chronic M. avium infection.

* Corresponding author. Mailing address: Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag no. 6, Newtown, NSW, Australia 2042. Phone: 61-2-9515 5210. Fax: 61-2-9351 3968. E-mail: wbritton{at}medicine.usyd.edu.au.

Infection and Immunity, June 2000, p. 3090-3096, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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