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Infect. Immun. doi:10.1128/IAI.00244-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guerin

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Institute for Systems Biology, Seattle, WA, University of California San Francisco, San Francisco, CA

^* To whom correspondence should be addressed. Email: cclay{at}stanford.edu.

	Abstract

Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico were vaccinated with one of three different BCG strains (BCG-Brazil [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination, peripheral blood mononuclear cells (PBMC) were obtained and recall immune responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis (Mtb) were evaluated using quantitative real time PCR. CFP activated PBMC from BBCG and DBCG immunized children expressed high levels of cytokines characteristic of an adaptive immune response (IFN-, IL-12 and IL-27) while those from children immunized with JBCG did not. In contrast, vaccination with JBCG resulted in significantly greater expression of cytokines characteristic of a proinflammatory immune response (IL-1, IL-1,, IL-6 and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated with BBCG or DBCG. Thus, different strains of BCG can activate different immune pathways that may affect long-term vaccine efficacy.