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Infection and Immunity, November 2008, p. 5181-5190, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00189-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Vaccination of Mice with a Yop Translocon Complex Elicits Antibodies That Are Protective against Infection with F1^– Yersinia pestis

Maya I. Ivanov, Betty L. Noel, Ryan Rampersaud, Patricio Mena, Jorge L. Benach, and James B. Bliska^*

Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794-5222

Received 11 February 2008/ Returned for modification 14 March 2008/ Accepted 6 August 2008

Yersinia pestis, the bacterial agent of plague, secretes several proteins important for pathogenesis or host protection. The F1 protein forms a capsule on the bacterial cell surface and is a well-characterized protective antigen but is not essential for virulence. A type III secretion system that is essential for virulence exports Yop proteins, which function as antiphagocytic or anti-inflammatory factors. Yop effectors (e.g., YopE) are delivered across the host cell plasma membrane by a translocon, composed of YopB and YopD. Complexes of YopB, YopD, and YopE (BDE) secreted by Yersinia pseudotuberculosis were purified by affinity chromatography and used as immunogens to determine if antibodies to the translocon could provide protection against Y. pestis in mice. Mice vaccinated with BDE generated high-titer immunoglobulin G antibodies specific for BDE, as shown by enzyme-linked immunosorbent assay and immunoblotting, and were protected against lethal intravenous challenge with F1^– but not F1⁺ Y. pestis. Mice passively immunized with anti-BDE serum were protected from lethal challenge with F1^– Y. pestis. The YopB protein or a complex of YopB and YopD (BD) was purified and determined by vaccination to be immunogenic in mice. Mice actively vaccinated with BD or passively vaccinated with anti-BD serum were protected against lethal challenge with F1^– Y. pestis. These results indicate that anti-translocon antibodies can be used as immunotherapy to treat infections by F1^– Y. pestis.

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* Corresponding author. Mailing address: Center for Infectious Diseases, SUNY Stony Brook, Stony Brook, NY 11794-5222. Phone: (631) 632-8782. Fax: (631) 632-4294. E-mail: jbliska{at}ms.cc.sunysb.edu

Published ahead of print on 2 September 2008.

Editor: B. A. McCormick

Present address: Columbia University College of Physicians and Surgeons, 630 West 168^th St., New York, NY 10032.

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Infection and Immunity, November 2008, p. 5181-5190, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00189-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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