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Infection and Immunity, January 2005, p. 250-257, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.250-257.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants for Mycobacterium tuberculosis Multivalent Acellular Vaccine

Avi-Hai Hovav, Yolanta Fishman, and Herve Bercovier*

Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel

Received 11 July 2004/ Returned for modification 7 September 2004/ Accepted 24 September 2004

In this study, we examined the immunogenicity and protective efficacy of six immunodominant Mycobacterium tuberculosis recombinant antigens (85B, 38kDa, ESAT-6, CFP21, Mtb8.4, and 16kDa) in a multivalent vaccine preparation (6Ag). Gamma interferon (IFN-{gamma}) and monophosphoryl lipid A-trehalose dicorynomycolate (Ribi) adjuvant systems were used separately or in combination for immunization with the recombinant antigens. Our results demonstrate that immunization of mice with Ribi emulsified antigens in the presence of IFN-{gamma} (Ribi+6Ag+IFN-{gamma}) resulted after challenge with a virulent M. tuberculosis strain in a significant reduction in the CFU counts that was comparable to that achieved with the BCG vaccine (~0.9-log protection). Antigen-specific immunoglobulin G (IgG) titers in the Ribi+6Ag+IFN-{gamma}-immunized mice were lower than in mice immunized with Ribi+6Ag and were oriented toward a Th1-type response, as confirmed by elevated IgG2a levels. In addition, splenocyte proliferation, IFN-{gamma} secretion, and NO production were significantly higher in splenocytes derived from Ribi+6Ag+IFN-{gamma}-immunized mice, whereas IL-10 secretion was decreased. These findings confirm the induction of a strong cellular immunity in the vaccinated mice that correlates well with their enhanced resistance to M. tuberculosis. The adjuvant effect of IFN-{gamma} was dose dependent. A dose of 5 µg of IFN-{gamma} per mouse per immunization gave optimal protection, whereas lower or higher amounts (0.5 or 50 µg/ mouse) of IFN-{gamma} failed to enhance protection.

* Corresponding author. Mailing address: Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, Jerusalem, P.O.B. 12272, Israel. Phone: 972-2-6758256. Fax: 972-2-6784010. E-mail: hb{at}cc.huji.ac.il.

Editor: F. C. Fang

Infection and Immunity, January 2005, p. 250-257, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.250-257.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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