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Clinical and Developmental Immunology
Volume 2011 (2011), Article ID 730702, 8 pages
http://dx.doi.org/10.1155/2011/730702
Research Article

Recombinant HBHA Boosting Effect on BCG-Induced Immunity against Mycobacterium tuberculosis Infection

G. G. Guerrero1,2,3,4,5 and C. Locht1,2,3,4

1INSERM U1019, Lille, France
2CNRS UMR8204, Lille, France
3Institut Pasteur de Lille, Lille, France
4Université Lille Nord de France, Lille, 59000, France
5Facultad de Ciencias Químicas, UJED, Gómez Palacio, DGO. 35060, Mexico

Received 14 September 2010; Revised 18 December 2010; Accepted 1 February 2011

Academic Editor: Nathalie Winter

Copyright © 2011 G. G. Guerrero and C. Locht. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Heterologous prime-boost regimens are effective strategies to promote long-term memory and strong cellular Th1 responses to Mycobacterium tuberculosis, when BCG is used in the priming step. Subcutaneous or intranasal boosting of BCG-vaccinated newborn mice with native heparin-binding haemagglutinin (nHBHA) significantly enhances protection against M. tuberculosis. However, nHBHA is characterized by a complex methylation pattern in its C-terminal domain, which is important for protective immunogenicity in primary vaccination. In this study we addressed the question whether boosting with recombinant, non-methylated HBHA (rHBHA) produced in Escherichia coli may enhance protection of BCG-primed newborn mice. We found that while subcutaneous rHBHA boosting enhanced protection of BCG-primed mice against intranasal M. tuberculosis infection both in spleen and lungs, enhanced protection against aerosol infection was only seen in the spleen (0.72 logs; ) but not in the lungs. Thus, in BCG-primed mice the methylation of the C-terminal domain of HBHA is dispensable for the induction of enhanced protection in the lungs against intranasal but not aerosol infection, whereas it enhances protection in the spleen in both challenge models. This report thus provides evidence that rHBHA may be considered as a booster vaccine against disseminated tuberculosis.