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Infection and Immunity, February 2000, p. 791-795, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

ESAT-6 Subunit Vaccination against Mycobacterium tuberculosis

Lise Brandt, Martin Elhay,dagger Ida Rosenkrands, Erik B. Lindblad, and Peter Andersen*

Department of TB Immunology, Statens Serum Institut, Copenhagen, Denmark

Received 19 July 1999/Returned for modification 13 September 1999/Accepted 8 November 1999

The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines. Here we demonstrate that, whereas immune responses to both short-term-culture filtrate and Ag85B are efficiently induced with DDA, this adjuvant was inefficient for the induction of immune responses to ESAT-6. Therefore, we investigated the modulatory effect of monophosphoryl lipid A (MPL), an immunomodulator which in different combinations has demonstrated strong adjuvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination of MPL and DDA elicited a strong ESAT-6-specific T-cell response and protective immunity comparable to that achieved with Mycobacterium bovis BCG.

* Corresponding author. Mailing address: Statens Serum Institut, Department of TB Immunology, Artillerivej 5, 2300 Copenhagen S., Denmark. Phone: 45 32683480. Fax: 45 32683035. E-mail: pa{at}ssi.dk.

dagger Present address: Novel Vaccines Laboratory, CSL Limited, Parkville, Victoria, Australia.

Infection and Immunity, February 2000, p. 791-795, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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