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Infection and Immunity, July 2007, p. 3658-3664, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00244-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guérin{triangledown}

Bo Wu,1 Chunhong Huang,1 Lourdes Garcia,2 Alfredo Ponce de Leon,3 Jose Sifuentes Osornio,3 Miriam Bobadilla-del-Valle,3 Leticia Ferreira,2 Sergio Canizales,2 Peter Small,4 Midori Kato-Maeda,5 Alan M. Krensky,1 and Carol Clayberger1*

Department of Pediatrics, Stanford University School of Medicine, Stanford, California,1 Instituto Nacional de Salud Publica, Cuernavaca, Morelos,2 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico,3 Institute for Systems Biology, Seattle, Washington,4 University of California San Francisco, San Francisco, California5

Received 14 February 2007/ Returned for modification 8 April 2007/ Accepted 2 May 2007

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 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 (gamma interferon, interleukin-2ß [IL-12ß], 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{alpha}, IL-1ß, 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, which may affect long-term vaccine efficacy.

* Corresponding author. Mailing address: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5164. Phone: (650) 725-3279. Fax: (650) 498-6077. E-mail: cclay{at}stanford.edu

{triangledown} Published ahead of print on 14 May 2007.

Editor: J. L. Flynn

Infection and Immunity, July 2007, p. 3658-3664, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00244-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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