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...

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]
  2. Kawamura A, Tanaka H, Tamura A, , 1995. Tsutsugamushi Disease. Tokyo: University of Tokyo Press.
  3. Kumar K, Saxena VK, Thomas TG, Lal S, , 2004. Outbreak investigation of scrub typhus in Himachal Pradesh (India). J Commun Dis 36: 277283.
  4. Chang W-H, , 1995. Current status of tsutsugamushi disease in Korea. J Korean Med Sci 10: 227238.[Crossref]
  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.
  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.
  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.
  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]
  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]
  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.
  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]
  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.
  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]
  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]
  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]
  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]
  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.
  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]
  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.
  20. Smadel JE, Ley HL, Diercks FH, Traub R, , 1950. Immunity in scrub typhus: resistance to induced reinfection. Arch Pathol (Chic) 50: 847861.
  21. Jerrells TR, Osterman JV, , 1982. Host defenses in experimental scrub typhus: deplayed-type hypersensitivity responses of inbred mice. Infect Immun 35: 117123.
  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.
  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.
  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]
  25. Hanson BA, , 1983. Effect of immune serum on infectivity of Rickettsia tsutsugamushi . Infect Immun 42: 341349.
  26. Kekcheyeva N, , 1968. Preventive immunization against tsutsugamushi fever. J Hyg Epidemiol Microbiol Immunol 12: 1417.
  27. Eisenberg GHG, Osterman JV, , 1977. Experimental scrub typhus immunogens: gamma-irradiated and formalinized rickettsiae. Infect Immun 15: 124131.
  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]
  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.
  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]
  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.
  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.
  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.
  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]
  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]
  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.
  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]
  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]
  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.
  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]

Data & Media loading...

  • Received : 30 Sep 2010
  • Accepted : 10 Mar 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