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Infection and Immunity, January 2009, p. 223-231, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00526-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Immunogenicity and Protective Efficacy of "Mycobacterium w" against Mycobacterium tuberculosis in Mice Immunized with Live versus Heat-Killed M. w by the Aerosol or Parenteral Route{triangledown}

Ankan Gupta,1,{dagger} Nishamol Geetha,1,{dagger},{ddagger} Jiju Mani,1 Pramod Upadhyay,1 V. M. Katoch,2 M. Natrajan,2 U. D. Gupta,2 and Sangeeta Bhaskar1*

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India,1 National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, UP 282001, India2

Received 29 April 2008/ Returned for modification 23 June 2008/ Accepted 26 October 2008

As the disease caused by Mycobacterium tuberculosis continues to be a burden, there is a concerted effort to find new vaccines to combat this problem. One of the important vaccine strategies is whole bacterial vaccines. This approach relies on multiple antigens and built-in adjuvanticity. Other mycobacterial strains which share cross-reactive antigens with M. tuberculosis have been considered as alternatives to M. bovis for vaccine use. One such strain, "Mycobacterium w", had been evaluated for its immunomodulatory properties in leprosy. A vaccine against leprosy based on killed M. w is approved for human use, where it has resulted in clinical improvement, accelerated bacterial clearance, and increased immune responses to Mycobacterium leprae antigens. M. w shares antigens not only with M. leprae but also with M. tuberculosis, and initial studies have shown that vaccination with killed M. w induces protection against tuberculosis in Mycobacterium bovis BCG responder, as well as BCG nonresponder, strains of mice. Hence, we further studied the protective potential of M. w and the underlying immune responses in the mouse model of tuberculosis. We analyzed the protective efficacy of M. w immunization in both live and killed forms through the parenteral route and by aerosol immunization, compared with that of BCG. Our findings provide evidence that M. w has potential protective efficacy against M. tuberculosis. M. w activates macrophage activity, as well as lymphocytes. M. w immunization by both the parenteral route and aerosol adminstration gives higher protection than BCG given by the parenteral route in the mouse model of tuberculosis.

* Corresponding author. Mailing address: Product Development Cell, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India. Phone: 91-11-26703670. Fax: 91-11-26162125. E-mail: sangeeta{at}nii.res.in

{triangledown} Published ahead of print on 3 November 2008.

Editor: J. L. Flynn

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Department of Vascular Biology. Medical University of Vienna, 1090 Vienna, Austria.

Infection and Immunity, January 2009, p. 223-231, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00526-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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