Volume 84, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



, the etiologic agent of scrub typhus, has a highly expressed and immunodominant 56-kD outer membrane protein. This protein is one of the leading candidates for diagnosis and vaccine development for scrub typhus. Previous studies using recombinant 56-kD protein (r56s) derived from Karp strain (Kpr56) in a mouse model have shown good homologous protection but only moderate to poor heterologous protection. We evaluated the cross-reactivity of recombinant 56-kD proteins from Karp, Kato, Gilliam, TA763, and three chimeric 56-kD proteins. Not all r56s are equally reactive with strain-specific serum samples. These data provide a first glance of how reactive these r56s are toward the antiserum of different strains and which r56 exhibits the broadest reactivity. A formulation of this combination has the potential to provide broad protection against the heterologous challenge and to be used in a highly sensitive diagnostic assay.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Brown GW, Robinson DM, Huxsoll DL, Ng TS, Lim KJ, Sannasey G, , 1976. Scrub typhus: a common cause of illness in indigenous populations. Trans R Soc Trop Med Hyg 70: 444448.[Crossref] [Google Scholar]
  2. Kawamura A, Tanaka H, Tamura A, , 1995. Tsutsugamushi Disease. Tokyo: University of Tokyo Press. [Google Scholar]
  3. Kumar K, Saxena VK, Thomas TG, Lal S, , 2004. Outbreak investigation of scrub typhus in Himachal Pradesh (India). J Commun Dis 36: 277283. [Google Scholar]
  4. Chang W-H, , 1995. Current status of tsutsugamushi disease in Korea. J Korean Med Sci 10: 227238.[Crossref] [Google Scholar]
  5. Jiang J, Marienau KJ, May LA, Beecham HJ, Wilkinson R, Ching W-M, Richards AL, , 2003. Laboratory diagnosis of two scrub typhus outbreaks at Camp Fuji, Japan in 2000 and 2001 by enzyme-linked immunosorbent assay, rapid flow assay, and Western blot assay using outer membrane 56-kD recombinant proteins. Am J Trop Med Hyg 69: 6066. [Google Scholar]
  6. Sharma A, Mahajan S, Gupta ML, Kanga A, Sharma V, , 2005. Investigation of an outbreak of scrub typhus in the himalayan region of India. Jpn J Infect Dis 58: 208210. [Google Scholar]
  7. Wang S, Huang J, Peng G, Jiang P, Zheng N, Liu J, Zhu S, Wang Z, , 2002. Natural foci of tsutsugamushi disease in the Nan Peng Lie Islands in China. Chin Med J (Engl) 115: 272275. [Google Scholar]
  8. Lewis MD, Yousuf AA, Lerdthusnee K, Razee A, Chandranoi K, Jones JW, , 2003. Scrub typhus reemergence in the Maldives. Emerg Infect Dis 9: 16381641.[Crossref] [Google Scholar]
  9. Durand AM, Kuartei S, Togamae I, Sengebau M, Demma L, Nicholson W, O'Leary M, , 2004. Scrub typhus in the Republic of Palau, Micronesia. Emerg Infect Dis 10: 18381840.[Crossref] [Google Scholar]
  10. Tay ST, Kamalanathan M, Rohani MY, , 2003. Antibody prevalence of Orientia tsutsugamushi, Rickettsia typhi and TT118 spotted fever group rickettsiae among Malaysian blood donors and febrile patients in the urban areas. Southeast Asian J Trop Med Public Health 34: 165170. [Google Scholar]
  11. Odorico DM, Graves SR, Currie B, Catmull J, Nack Z, Ellis S, Wang L, Miller DJ, , 1998. New Orientia tsutsugamushi strain from scrub typhus in Australia. Emerg Infect Dis 4: 641644.[Crossref] [Google Scholar]
  12. Lee YS, Wang PH, Tseng SJ, Ko CF, Teng HJ, , 2006. Epidemiology of scrub typhus in eastern Taiwan, 2000–2004. Jpn J Infect Dis 59: 235238. [Google Scholar]
  13. Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, Teja-Isavadham P, Bhodhidatta K, Corcoran KD, Dasch GA, Strickman D, , 1996. Scrub typhus poorly responsive to antibiotics in northern Thailand. Lancet 348: 8689.[Crossref] [Google Scholar]
  14. Mathai E, Rolain JM, Verghese GM, Abraham OC, Mathai D, Mathai M, Raoult D, , 2003. Outbreak of scrub typhus in southern India during the cooler months. Ann N Y Acad Sci 990: 359364.[Crossref] [Google Scholar]
  15. Bell EJ, Bennett LF, Whiteman L, , 1946. Antigenic differences between strains of scrub typhus as demonstrated by cross neutralization tests. Proc Soc Exp Biol Med 62: 134137.[Crossref] [Google Scholar]
  16. Rights FL, Smadel JE, Jackson EB, , 1948. Studies on scrub typhus (tsutsugamushi disease). Part III: Heterogeneity of strains of Rickettsia tsutsugamushi as demonstrated by cross vaccination studies. J Exp Med 87: 339351.[Crossref] [Google Scholar]
  17. Bennett LF, Patt JK, Hopps HE, , 1949. Studies on scrub typhus (tsutsugamushi disease). Part IV: Heterogeneity of strains of R. tsutsugamushi as demonstrated by cross-neutralization tests. J Immunol 62: 453461. [Google Scholar]
  18. Kang JS, Chang WH, , 1999. Antigenic relationship among the eight prototype and new serotype strains of Orientia tsutsugamushi revealed by monoclonal antibodies. Microbiol Immunol 43: 229234.[Crossref] [Google Scholar]
  19. Smadel JE, Ley HL, Diercks FH, Paterson PY, Wisseman CL, Traub R, , 1952. Immunization against scrub typhus: duration of immunity in volunteers following combined living vaccine and chemoprophylaxis. Am J Trop Med Hyg 1: 8799. [Google Scholar]
  20. Smadel JE, Ley HL, Diercks FH, Traub R, , 1950. Immunity in scrub typhus: resistance to induced reinfection. Arch Pathol (Chic) 50: 847861. [Google Scholar]
  21. Jerrells TR, Osterman JV, , 1982. Host defenses in experimental scrub typhus: deplayed-type hypersensitivity responses of inbred mice. Infect Immun 35: 117123. [Google Scholar]
  22. Jerrells TR, Osterman JV, , 1983. Development of specific and crossreactive lymphocyte proliferative responses during chronic immunizing infections with Rickettsia tsutsugamushi . Infect Immun 40: 147156. [Google Scholar]
  23. Hickman CJ, Stover CK, Joseph SW, Oaks EV, , 1993. Murine T-cell response to native and recombinant protein antigens of Rickettsia tsutsugamushi . Infect Immun 61: 16741681. [Google Scholar]
  24. Seong SY, Kim MK, Lee SM, Odgerel Z, Choi MS, Han TH, Kim IS, Kang JS, Lim BU, , 2000. Neutralization epitopes on the antigenic domain II of the Orientia tsutsugamushi 56-kDa protein revealed by monoclonal antibodies. Vaccine 19: 29.[Crossref] [Google Scholar]
  25. Hanson BA, , 1983. Effect of immune serum on infectivity of Rickettsia tsutsugamushi . Infect Immun 42: 341349. [Google Scholar]
  26. Kekcheyeva N, , 1968. Preventive immunization against tsutsugamushi fever. J Hyg Epidemiol Microbiol Immunol 12: 1417. [Google Scholar]
  27. Eisenberg GHG, Osterman JV, , 1977. Experimental scrub typhus immunogens: gamma-irradiated and formalinized rickettsiae. Infect Immun 15: 124131. [Google Scholar]
  28. Choi Y, Kim KS, Kim TY, Cheong HS, Ahn BY, , 2006. Long-term egg-yolk adaptation of the Orientia tsutsugamushi for preparation of a formalinized immunogen. Vaccine 24: 14381445.[Crossref] [Google Scholar]
  29. Tamura A, Sakurami H, Takahashi K, Oyanagi M, , 1985. Analysis of polypeptide composition and antigenic components of Rickettsia tsutsugamushi by polyacrylamide gel electrophoresis and immunoblotting. Infect Immun 48: 671675. [Google Scholar]
  30. Ohashi N, Tamura A, Suto T, , 1988. Immunoblotting analysis of anti-rickettsial antibodies produced in patients of tsutsugamushi disease. Microbiol Immunol 32: 10851092.[Crossref] [Google Scholar]
  31. Tay ST, Rohani MY, Ho TM, Devi S, , 2002. Antigenic types of Orientia tsutsugamushi in Malaysia. Southeast Asian J Trop Med Public Health 33: 557564. [Google Scholar]
  32. Seong SY, Huh MS, Jang WJ, Park SG, Kim JG, Woo SG, Choi MS, Kim IS, Chang WH, , 1997. Induction of homologous immune response to Rickettsia tsutsugamushi Boryong with partial 56-kilodalton recombinant antigen fused with the maltose-binding protein MBP-Bor56. Infect Immun 65: 15411545. [Google Scholar]
  33. Yu Y, Wen B, Wen B, Niu D, Chen M, Qiu L, , 2005. Induction of protective immunity against scrub typhus with a 56-kilodalton recombinant antigen fused with a 47-kilodalton antigen of Orientia tsutsugamushi Karp. Am J Trop Med Hyg 72: 458464. [Google Scholar]
  34. Kaminski RW, Turbyfill KR, Chao CC, Ching WM, Oaks EV, , 2009. Mucosal Adjuvanticity of a Shigella Invasin complex with DNA-based vaccines. Clin Vaccine Immunol 16: 574586.[Crossref] [Google Scholar]
  35. Seong SY, Kim HR, Huh MS, Park SG, Kang JS, Han TH, Choi MS, Chang WH, Kim IS, , 1997. Induction of neutralizing antibody in mice by immunization with recombinant 56 kDa protein of Orientia tsutsugamushi . Vaccine 15: 741747.[Crossref] [Google Scholar]
  36. Moree MF, , 1992. Structural, antigenic, and biological characterization of Rickettsia tsutsugamushi antigenic proteins. Ph.D. Dissertation. Baltimore, MD: Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore. [Google Scholar]
  37. Chattopadhyay S, Jiang J, Chan TC, Manetz TS, Chao CC, Ching WM, Richards AL, , 2005. Scrub typhus vaccine candidate Kp r56 induces humoral and cellular immune responses in cynomolgus monkeys. Infect Immun 73: 50395047.[Crossref] [Google Scholar]
  38. Shirai A, Robinson DM, Brown GW, Gan E, Huxsoll DL, , 1979. Antigenic analysis by direct immunofluorescence of 114 isolates of Rickettsia tsutsugamushi recovered from febrile patients in rural Malaysia. Jpn J Med Sci Biol 32: 337344.[Crossref] [Google Scholar]
  39. Ni YS, Chan TC, Chao CC, Richards AL, Dasch GA, Ching WM, , 2005. Protection against scrub typhus by a plasmid vaccine encoding the 56-KD outer membrane protein antigen gene. Am J Trop Med Hyg 73: 936941. [Google Scholar]
  40. Chao CC, Zhang Z, Wang H, Alkhalil A, Ching WM, , 2008. Serological reactivity and biochemical characterization of methylated and unmethylated forms of a recombinant protein fragment derived from outer membrane protein B of Rickettsia typhi . Clin Vaccine Immunol 15: 684690.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 30 Sep 2010
  • Accepted : 10 Mar 2011
  • Published online : 01 Jun 2011

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error