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Infection and Immunity, June 2007, p. 2841-2852, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.02029-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Identification of In Vivo-Expressed Immunogenic Proteins by Serological Proteome Analysis of the Bacillus anthracis Secretome{triangledown} ,{dagger}

Theodor Chitlaru, Orit Gat, Haim Grosfeld, Itzhak Inbar, Yael Gozlan, and Avigdor Shafferman*

Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel

Received 27 December 2006/ Returned for modification 15 February 2007/ Accepted 4 March 2007

In a previous comparative proteomic study of Bacillus anthracis examining the influence of the virulence plasmids and of various growth conditions on the composition of the bacterial secretome, we identified 64 abundantly expressed proteins (T. Chitlaru, O. Gat, Y. Gozlan, N. Ariel, and A. Shafferman, J. Bacteriol. 188:3551-3571, 2006). Using a battery of sera from B. anthracis-infected animals, in the present study we demonstrated that 49 of these proteins are immunogenic. Thirty-eight B. anthracis immunogens are documented in this study for the first time. The relative immunogenicities of the 49 secreted proteins appear to span a >10,000-fold range. The proteins eliciting the highest humoral response in the course of infection include, in addition to the well-established immunogens protective antigen (PA), Sap, and EA1, GroEL (BA0267), AhpC (BA0345), MntA (BA3189), HtrA (BA3660), 2,3-cyclic nucleotide diesterase (BA4346), collagen adhesin (BAS5205), an alanine amidase (BA0898), and an endopeptidase (BA1952), as well as three proteins having unknown functions (BA0796, BA0799, and BA0307). Of these 14 highly potent secreted immunogens, 11 are known to be associated with virulence and pathogenicity in B. anthracis or in other bacterial pathogens. Combining the results reported here with the results of a similar study of the membranal proteome of B. anthracis (T. Chitlaru, N. Ariel, A. Zvi, M. Lion, B. Velan, A. Shafferman, and E. Elhanany, Proteomics 4:677-691, 2004) and the results obtained in a functional genomic search for immunogens (O. Gat, H. Grosfeld, N. Ariel, I. Inbar, G. Zaide, Y. Broder, A. Zvi, T. Chitlaru, Z. Altboum, D. Stein, S. Cohen, and A. Shafferman, Infect. Immun. 74:3987-4001, 2006), we generated a list of 84 in vivo-expressed immunogens for future evaluation for vaccine development, diagnostics, and/or therapeutic intervention. In a preliminary study, the efficacies of eight immunogens following DNA immunization of guinea pigs were compared to the efficacy of a PA DNA vaccine. All eight immunogens induced specific high antibody titers comparable to the titers elicited by PA; however, unlike PA, none of them provided protection against a lethal challenge (50 50% lethal doses) of virulent B. anthracis strain Vollum spores.

* Corresponding author. Mailing address: Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel. Phone: 972-8-9381595. Fax: 972-8-9401404. E-mail: avigdors{at}iibr.gov.il

{triangledown} Published ahead of print on 12 March 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: D. L. Burns

Infection and Immunity, June 2007, p. 2841-2852, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.02029-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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