title: Protective immunity of 56-kDa type-specific antigen of Orientia tsutsugamushi causing scrub typhus.
abstract: Scrub typhus, caused by infection with Orientia tsutsugamushi, is a mite-borne zoonotic disease endemic to the Asian-Pacific region. In Korea, the incidence of this disease has increased with climate changes, and over 10,000 cases of infection were reported in 2013. Although this infection is treatable with antibiotics such as doxycycline and azithromycin, an effective prophylactic vaccine against O. tsutsugamushi would be more desirable for preventing scrub typhus in endemic areas. In this study, we investigated the 56-kDa type-specific antigen (TSA56), which is a major outer membrane protein of O. tsutsugamushi, as a vaccine candidate. Intranasal immunization of recombinant TSA56 (rec56) induced a higher level of TSA56- specific IgG than that induced by intramuscular immunization of tsa56-expressing DNA (p56). Both types of immunization induced a cell-mediated immune response to TSA56, as demonstrated by the splenic cell proliferation assay. Mice immunized with p56, followed by rec56 plus heat-labile enterotoxin B subunit from E. coli, had a stronger protection from a homologous challenge with the O. tsutsugamushi Boryong strain than with other combinations. Our preliminary results suggest that an effective human vaccine for scrub typhus can include either recombinant TSA56 protein or tsa56-expressing DNA, and provide the basis for further studies to optimize vaccine performance using additional antigens or different adjuvants.
authors.affiliation: Division of Zoonoses, Center for Immunology and Pathology, Korea National Institute of Health, Korea Centers for Diseases Control and Prevention, Cheongju 363-700, Republic of Korea.
authors.forename: Sangho
authors.initials: S
authors.lastname: Choi
authors.forename: Hang Jin
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Ju
authors.forename: Byoungchul
authors.initials: B
authors.lastname: Gill
authors.forename: Kyu-Jam
authors.initials: KJ
authors.lastname: Hwang
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage; D029968:Escherichia coli Proteins / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012285:Orientia tsutsugamushi / Q000276:immunology*; D012612:Scrub Typhus / Q000276:immunology / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D008565:Membrane Proteins; C064828:Sta56 antigen, Rickettsia tsutsugamushi; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli