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Am. J. Trop. Med. Hyg., 73(5), 2005, pp. 936-941
Copyright © 2005 by The American Society of Tropical Medicine and Hygiene

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PROTECTION AGAINST SCRUB TYPHUS BY A PLASMID VACCINE ENCODING THE 56-KD OUTER MEMBRANE PROTEIN ANTIGEN GENE

YI-SHENG NI, TEIK-CHYE CHAN, CHIEN-CHUNG CHAO, ALLEN L. RICHARDS, GREGORY A. DASCH, AND WEI-MEI CHING*
Rickettsial Diseases Department, U.S. Naval Medical Research Center, Silver Spring, Maryland; Uniformed Services University of the Health Sciences, Bethesda, Maryland

The 56-kD outer membrane protein of Orientia tsutsugamushi has previously been shown to be the immunodominant antigen in scrub typhus infections. Its gene was cloned into the DNA vaccine vector pVR1012 as a vaccine candidate (pKarp56). The in vitro expression of this 56-kD antigen by pKarp56 was confirmed in tissue culture by an indirect fluorescence assay and Western blot analysis. The initial antibody responses of mice immunized with varied doses of the pKarp56 were barely detected, but increases were observed after each of three subsequent booster immunizations. Although no protection was observed with a single immunization of pKarp56, after four immunizations, 60% of the mice survived a 1,000 x 50% lethal dose (LD50) challenge. These results specifically confirm the importance of the 56-kD protein antigen in protective immunity against O. tsutsugamushi and demonstrate the feasibility of DNA vaccines for the prevention of scrub typhus.

Received January 19, 2005. Accepted for publication May 27, 2005.

Financial support: This work was supported by Work Unit Number 62787A.870.J.A0008 and 61152N.M40004.001.1608.

Disclaimer: The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Navy Department, the Army Department, or the Department of Defense at large.

* Address correspondence to Wei-Mei Ching, Rickettsial Diseases Department, Infectious Diseases Directorate, U.S. Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500. E-mail: chingw{at}nmrc.navy.mil

Authors’ addresses: Yi-Sheng Ni, Food and Drug Administration/Center for Biologics Evaluation and Research, Building 29, Room 525, 8800 Rockville Pike, Bethesda, MD 20892. Teik-Chye Chan, Chien-Chung Chao, Allen L. Richards, and Wei-Mei Ching, Rickettsial Diseases Department, Infectious Diseases Directorate, U.S. Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, Telephone: 301-319-7438, Fax: 301-319-7460, E-mail: chingw{at}nmrc.navy.mil. Gregory A. Dasch, Viral and Rickettsial Zoonoses Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Mailstop G-13, Atlanta, GA 30333.






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