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Infection and Immunity, June 2009, p. 2311-2319, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01298-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of Cross-Reactive Epitopes on the Conserved 47-Kilodalton Antigen of Orientia tsutsugamushi and Human Serine Protease{triangledown}

Hua-Wei Chen,1,2 Zhiwen Zhang,1,2 Erin Huber,1,2 Chien-Chung Chao,1 Hui Wang,1,2 Gregory A. Dasch,3 and Wei-Mei Ching1,2*

Naval Medical Research Center, Silver Spring, Maryland,1 Uniformed Services University of the Health Sciences, Bethesda, Maryland,2 National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia3

Received 23 October 2008/ Returned for modification 27 November 2008/ Accepted 7 March 2009

Orientia tsutsugamushi is the causative agent of scrub typhus. One of the protein antigens of this species, the conserved 47-kDa protein (HtrA), has been shown to induce an antibody response in patients and can provide protective immunity against live challenge by Orientia in mice. Pepscan experiments identified many peptide epitope clusters in different parts of this protein. The majority of the most reactive epitopes are located at the C terminus of the protein (from amino acid 333 to amino acid 430). Protein sequence analysis revealed that the 47-kDa protein contains a trypsin domain and has sequence homology to human serine protease HtrA1 (hHtrA1). As the 47-kDa protein is a potential vaccine candidate and its ability to induce autoimmunity is a concern, the reactivity of scrub typhus patient sera with purified recombinant 47-kDa and hHtrA1 proteins was tested. A significant percentage (>20%) of scrub typhus patient sera reacted strongly with recombinant hHTRA1 and two of the antigenic polypeptide epitopes in hHtrA1. These findings suggest that the safety of the full-length 47-kDa antigen as a vaccine candidate is a significant issue due to its cross-reactivity with a human protein, which may also contribute to autoimmune responses or enhanced pathology in some scrub typhus patients.

* Corresponding author. Mailing address: Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910. Phone: (301) 319-7438. Fax: (301) 319-7451. E-mail: wei.ching{at}med.navy.mil

{triangledown} Published ahead of print on 16 March 2009.

Editor: A. Camilli

Infection and Immunity, June 2009, p. 2311-2319, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01298-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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