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Infection and Immunity, January 2007, p. 408-416, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01290-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Combined CTA1-DD/ISCOMs Vector Is an Effective Intranasal Adjuvant for Boosting Prior Mycobacterium bovis BCG Immunity to Mycobacterium tuberculosis{triangledown}

Claire Swetman Andersen,1,{dagger} Jes Dietrich,1* Else Marie Agger,1 Nils Y. Lycke,2 Karin Lövgren,3 and Peter Andersen1

Statens Serum Institute, Adjuvant/Vaccine Research, Department of Infectious Disease Immunology, Copenhagen, Denmark,1 Department of Clinical Immunology, MIVAC, University of Göteborg, Göteborg, Sweden,2 Isconova, Uppsala, Sweden3

Received 11 August 2006/ Returned for modification 9 October 2006/ Accepted 20 October 2006

Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains one of the leading causes of mortality worldwide. The current "gold standard" vaccine Mycobacterium bovis BCG has a limited efficacy that wanes over time. The development of a vaccine to boost BCG-induced immunity is therefore a highly active area of research. Mucosal administration of vaccines is believed to provide better protection against pathogens, such as M. tuberculosis, that invade the host via mucosal surfaces. In this study we demonstrate that an intranasal vaccine, comprising the antigenic fusion protein Ag85B-ESAT-6 and the mucosal combined adjuvant vector CTA1-DD/ISCOMs, strongly promotes a Th1-specific immune response, dominated by gamma interferon-secreting CD4-positive T cells. Mucosal administration of Ag85B-ESAT-6 mixed with CTA1-DD/ISCOMs strongly boosted prior BCG immunity, leading to a highly increased recruitment of antigen-specific cells to the site of infection. Most importantly, we observed a significantly (P < 0.001) reduced bacterial burden in the lung compared to nonboosted control animals. Thus, the results demonstrate the effectiveness of mucosal vaccination with Ag85B-ESAT-6 mixed with CTA1-DD/ISCOMs as adjuvant for stimulating TB-specific protective immunity in the lung.

* Corresponding author. Mailing address: Staten Serum Institute, TB Vaccine Research, Department of Infectious Disease Immunology, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. Phone: 45 32 68 38 19. Fax: 45 32 68 30 35. E-mail: JDI{at}ssi.dk.

{triangledown} Published ahead of print on 30 October 2006.

Editor: F. C. Fang

{dagger} Current address: Institut Pasteur, Dept. de Parasitologie, Unité de Parasitologie Biomédicale, 25-28, Rue du Docteur Roux, 75015 Paris, France.

Infection and Immunity, January 2007, p. 408-416, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01290-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Belyakov, I. M., Ahlers, J. D. (2009). What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?. J. Immunol. 183: 6883-6892 [Abstract] [Full Text]  
  • Sundling, C., Schon, K., Morner, A., Forsell, M. N. E., Wyatt, R. T., Thorstensson, R., Hedestam, G. B. K., Lycke, N. Y. (2008). CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization. J. Gen. Virol. 89: 2954-2964 [Abstract] [Full Text]  
  • Ciabattini, A., Pettini, E., Andersen, P., Pozzi, G., Medaglini, D. (2008). Primary Activation of Antigen-Specific Naive CD4+ and CD8+ T Cells following Intranasal Vaccination with Recombinant Bacteria. Infect. Immun. 76: 5817-5825 [Abstract] [Full Text]  


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