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Infection and Immunity, March 2004, p. 1608-1617, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1608-1617.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Combination of the Cationic Surfactant Dimethyl Dioctadecyl Ammonium Bromide and Synthetic Mycobacterial Cord Factor as an Efficient Adjuvant for Tuberculosis Subunit Vaccines

L. Holten-Andersen,{dagger} T. M. Doherty, K. S. Korsholm, and P. Andersen*

Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen, Denmark

Received 16 October 2003/ Returned for modification 13 November 2003/ Accepted 19 November 2003

Recombinant, immunodominant antigens derived from Mycobacterium tuberculosis can be used to effectively vaccinate against subsequent infection. However, the efficacy of these recombinant proteins is dependent on the adjuvant used for their delivery. This problem affects many potential vaccines, not just those for tuberculosis, so the discovery of adjuvants that can promote the development of cell-mediated immunity is of great interest. We have previously shown that the combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and the immunomodulator modified lipid A synergistically potentiates Th1 T-cell responses. Here we report a screening program for other adjuvants with reported Th1-promoting activity and identify a second novel adjuvant formulation that drives the development of Th1 responses with an extremely high efficacy. The combination of dimethyl dioctadecyl ammonium bromide and the synthetic cord factor trehalose dibehenate promotes strong protective immune responses, without overt toxicity, against M. tuberculosis infection in a vaccination model and thus appears to be a very promising candidate for the development of human vaccines.

* Corresponding author. Mailing address: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 81/301, DK-2300 Copenhagen S, Denmark. Phone: 45 32 68 34 62. Fax: 45 32 68 30 35. E-mail: pa{at}ssi.dk.

Editor: D. L. Burns

{dagger} Present address: Tumor Immunology Group, Danish Cancer Society, DK-2100 Copenhagen, Denmark.

Infection and Immunity, March 2004, p. 1608-1617, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1608-1617.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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