HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dietrich, J. Articles by Andersen, P. Search for Related Content PubMed PubMed Citation Articles by Dietrich, J. Articles by Andersen, P.

Synergistic Effect of Bacillus Calmette Guerin and a Tuberculosis Subunit Vaccine in Cationic Liposomes: Increased Immunogenicity and Protection¹

Department of Infectious Disease Immunology, Statens Serum Institute, Copenhagen, Denmark

In the present work, we evaluated a new TB vaccine approach based on a combination of the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine and a subunit vaccine consisting of the proteins Ag85B and ESAT-6. We demonstrate that in addition to its vaccine efficacy BCG is an immune modulator that can potentiate a Th1 immune response better than the well-known adjuvant mono phosphoryl lipid A, leading to enhanced recognition of the subunit vaccine Ag85B-ESAT-6. Importantly, adding a vehicle to the vaccine, such as the cationic liposome dimethyl dioctadecyl ammonium bromide (DDA), significantly increased the potentiating effect of BCG. This synergistic effect between BCG and Ag85B-ESAT-6/liposome required drainage to the same lymph node of all vaccine components but did not require direct mixing of the components and was therefore also observed when BCG and Ag85B-ESAT-6/liposome were given as separate injections at sites draining to the same lymph node. The resulting optimized vaccine protocol consisting of BCG and subunit in liposomes (injected side by side) followed by boosting with the subunit in conventional adjuvant resulted in an impressive increase in the protective efficacy of up to 7-fold compared with BCG alone and 3-fold compared with unaugmented BCG boosted by the subunit vaccine. Thus, these studies suggest an immunization strategy where a novel TB subunit vaccine is administered as part of the child vaccination program together with BCG in neonates and followed by subunit boosting.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was partially supported by the Danish Research Agency, Ministry of Science, Technology, and Innovation.

² Address correspondence and reprint requests to Dr. Jes Dietrich, Department of Infectious Disease Immunology, Statens Serum Institute, Artillerivej 5, Copenhagen Denmark. E-mail address: JDI{at}ssi.dk

³ Abbreviations used in this paper: TB, tuberculosis; BCG, bacillus Calmette-Guérin; ds, different site; MHC-II, MHC class II; MPL, monophosphoryl lipid A; M.tb, Mycobacterium tuberculosis; ss, side by side.