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Infection and Immunity, July 2003, p. 3894-3900, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3894-3900.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Tripalmitoyl-S-Glyceryl-Cysteine-Dependent OspA Vaccination of Toll-Like Receptor 2-Deficient Mice Results in Effective Protection from Borrelia burgdorferi Challenge

Alyson Yoder,¹ Xiaohui Wang,¹ Ying Ma,¹ Mario T. Philipp,² Marta Heilbrun,^1, John H. Weis,¹ Carsten J. Kirschning,³ R. Mark Wooten,⁴ and Janis J. Weis^1*

Department of Pathology, University of Utah, Salt Lake City, Utah 84132,¹ Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 70433,² Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany,³ Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614-5806⁴

Received 6 February 2003/ Returned for modification 20 March 2003/ Accepted 2 April 2003

Toll-like receptor 2 (TLR2) is a transmembrane signal transducer for tripalmitoyl-S-glyceryl-cysteine (Pam₃Cys)-modified lipoproteins, including OspA from the Lyme disease spirochete Borrelia burgdorferi. The Pam₃Cys modification provides adjuvant activity for inducing humoral responses, suggesting that TLR2 could function as the adjuvant receptor for the OspA vaccine. The importance of TLR2 in the humoral response to OspA was confirmed, because overall levels of immunoglobulin G (IgG) were reduced in TLR2-deficient mice, when compared with those in wild-type mice. However, the levels of production of IgG1 were similar in both mouse strains, and the levels of induction of protective immunity were comparable. Unlipidated OspA was not immunogenic in wild-type or TLR2-deficient mice, indicating the lipid modification was active in the absence of TLR2. These findings indicate that the Pam₃Cys modification of bacterial lipoprotein has adjuvant properties independent of TLR2 signaling.

Editor: F. C. Fang

Present address: Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157.

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