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Infection and Immunity, July 2001, p. 4329-4336, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4329-4336.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antigenic Diversity among Helicobacter pylori Vacuolating Toxins

Arlene D. Vinion-Dubiel,1 Mark S. McClain,2 Ping Cao,2 Raymond L. Mernaugh,3 and Timothy L. Cover1,2,4,*

Departments of Medicine,2 Microbiology and Immunology,1 and Biochemistry and the Vanderbilt-Ingram Cancer Center,3 Vanderbilt University School of Medicine, Nashville, Tennessee 37232, and Veterans Affairs Medical Center, Nashville, Tennessee 372124

Received 8 January 2001/Returned for modification 28 March 2001/Accepted 23 April 2001

Helicobacter pylori vacuolating cytotoxin (VacA) is a secreted protein that induces vacuolation of epithelial cells. To study VacA structure and function, we immunized mice with purified type s1-m1 VacA from H. pylori strain 60190 and generated a panel of 10 immunoglobulin G1kappa anti-VacA monoclonal antibodies. All of the antibodies reacted with purified native VacA but not with denatured VacA, suggesting that these antibodies react with conformational epitopes. Seven of the antibodies reacted with both native and acid-treated VacA, which suggests that epitopes present on both oligomeric and monomeric forms of the toxin were recognized. Two monoclonal antibodies, both reactive with epitopes formed by amino acids in the carboxy-terminal portion of VacA (amino acids 685 to 821), neutralized the cytotoxic activity of type s1-m1 VacA when toxin and antibody were mixed prior to cell contact but failed to neutralize the cytotoxic activity of type s1-m2 VacA. Only 3 of the 10 antibodies consistently recognized type s1-m1 VacA toxins from multiple H. pylori strains, and none of the antibodies recognized type s2-m2 VacA toxins. These results indicate that there is considerable antigenic diversity among VacA toxins produced by different H. pylori strains.

* Corresponding author. Mailing address: Division of Infectious Diseases, A3310 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232. Phone: (615) 322-2035. Fax: (615) 343-6160. E-mail: COVERTL{at}CTRVAX.VANDERBILT.EDU.

Infection and Immunity, July 2001, p. 4329-4336, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4329-4336.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • KI, M.-R., HONG, I.-H., PARK, J.-K., HONG, K.-S., HWANG, O.-K., HAN, J.-Y., JI, A.-R., PARK, S.-I., LEE, S.-K., YOO, S.-E., JEONG, K.-S. (2009). Potent Neutralization of Vacuolating Cytotoxin (VacA) of Helicobacter pylori by Immunoglobulins Against the Soluble Recombinant VacA. Anticancer Res 29: 2393-2402 [Abstract] [Full Text]  
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