A Field Trial of a Vaccine Prepared From the Volner Strain of Rickettsia Tsutsugamushi

Berge, Trygve; Gauld, Ross L.; Kitaoka, Masami

doi:10.1093/oxfordjournals.aje.a119366

Cited by 22 publications

(21 citation statements)

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“…The challenge of establishing a vaccine for scrub typhus caused by O. tsutsugamushi was embarked upon decades ago (3,6). The present work provides additional data that will help in this effort by describing for the first time the safety, immunogenicity, and efficacy of a recombinant scrub typhus vaccine candidate in a nonhuman primate model.…”

Section: Discussionmentioning

confidence: 99%

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Scrub Typhus Vaccine Candidate Kp r56 Induces Humoral and Cellular Immune Responses in Cynomolgus Monkeys

et al. 2005

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A truncated recombinant 56-kDa outer membrane protein of the Karp strain of Orientia tsutsugamushi (Kp r56) was evaluated in cynomolgus monkeys (Macaca fascicularis) for immunogenicity and safety as a vaccine candidate for the prevention of scrub typhus. This recombinant antigen induced strong humoral and cellular immune responses in two monkeys and was found to be well tolerated. Antigen-specific immunoglobulin M (IgM) and IgG were produced to almost maximal levels within 1 week of a single immunization. Peripheral blood mononuclear cells from vaccinated animals showed an induction of antigen-specific proliferation and gamma interferon production. The Kp r56 was not as efficient as infection with live organisms in preventing reinfection but was able to reduce the inflammation produced at the site of challenge. This report describes the results of the first systematic study of the immunogenicity of a recombinant scrub typhus vaccine candidate in a nonhuman primate model.

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Section: Discussionmentioning

confidence: 99%

“…Initial vaccine efforts with killed O. tsutsugamushi were successful in animals but not in human studies conducted in Burma and Japan (3,6). The failure of these vaccines in humans was most likely due to the inability of the killed organisms to stimulate long-lasting heterologous protection.…”

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confidence: 99%

Scrub Typhus Vaccine Candidate Kp r56 Induces Humoral and Cellular Immune Responses in Cynomolgus Monkeys

et al. 2005

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“…That isolate was subsequently used to prepare a lyophilized rat lung-spleen vaccine, the first US scrub typhus vaccine ever tested in a field trial (table 2). However, it proved to be unsuccessful [37,40,72]. Unlike during World War II, during the Vietnam conflict scrub typhus was of incidental concern in training areas [32,226].…”

Section: Geographic Distribution Of Antigenic Typesmentioning

confidence: 99%

“…The dramatic impact of the disease in the Asia-Pacific theater of the war drove the substantial effort during and immediately after the war to prevent, control, and treat the disease [35]. This program, coordinated by the US Typhus Commission, included development of treatments, novel miticides, impregnation of repellent in clothing, environmental control through burning and clearing of troop encampment areas, and one of the first substantial, although ultimately unsuccessful, vaccine trials [32,[36][37][38]. Unfortunately, the military relevance of this disease was painfully learned again !30 years later during the Vietnam conflict, when it was reported to be second only to malaria as a leading cause of fever among troops in the field [3,32,39].…”

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confidence: 99%

Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

et al. 2009

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Orientia tsutsugamushi is the etiological agent of scrub typhus, an acute, mite-borne, febrile illness that occurs in the Asia-Pacific region. Historically, strain characterization used serological analysis and revealed dramatic antigenic diversity. Eyeing a recommendation of potential vaccine candidates for broad protection, we review geographic diversity and serological and DNA prevalences. DNA analysis together with immunological analysis suggest that the prototype Karp strain and closely related strains are the most common throughout the region of endemicity. According to serological analysis, approximately 50% of isolates are seroreactive to Karp antisera, and approximately one-quarter of isolates are seroreactive to antisera against the prototype Gilliam strain. Molecular methods reveal greater diversity. By molecular methods, strains phylogenetically similar to Karp make up approximately 40% of all genotyped isolates, followed by the JG genotype group (Japan strains serotypically similar to the Gilliam strain but genetically non-Gilliam; 18% of all genotyped isolates). Three other genotype groups (Kato-related, Kawasaki-like, and TA763-like) each represent approximately 10% of genotyped isolates. Strains genetically similar to the Gilliam strain make up only 5% of isolates. Strains from these groups should be included in any potential vaccine.

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“…Approaches have included the use of formalin-killed bacteria [19,20], inoculation with viable organisms followed by antimicrobial treatment [21], irradiated Orientia tsutsugamushi [22], subunit vaccines [23,24], and DNA vaccine [25]. Most of the vaccine trials resulted in short-term protection (generally less than one year), immunity to only the homologous strain, or no significant outcomes, especially in human infections.…”

Section: Introductionmentioning

confidence: 99%

Immunization with an Autotransporter Protein of Orientia tsutsugamushi Provides Protective Immunity against Scrub Typhus

Sharma

Kim

et al. 2015

PLoS Negl Trop Dis

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BackgroundScrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Recently, the rapid increase of scrub typhus incidence in several countries within the endemic region has become a serious public health issue. Despite the wide range of preventative approaches that have been attempted in the past 70 years, all have failed to develop an effective prophylactic vaccine. Currently, the selection of the proper antigens is one of the critical barriers to generating cross-protective immunity against antigenically-variable strains of O. tsutsugamushi.Methodology/Principal FindingsWe examined the potential role of ScaA protein, an autotransporter protein of O. tsutsugamushi, in bacterial pathogenesis and evaluated the protective attributes of ScaA immunization in lethal O. tsutsugamushi infection in mice. Our findings demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA antibody significantly neutralizes bacterial infection of host cells. In addition, immunization with ScaA not only provides protective immunity against lethal challenges with the homologous strain, but also confers significant protection against heterologous strains when combined with TSA56, a major outer membrane protein of O. tsutsugamushi.Conclusions/SignificanceImmunization of ScaA proteins provides protective immunity in mice when challenged with the homologous strain and significantly enhanced protective immunity against infection with heterologous strains. To our knowledge, this is the most promising result of scrub typhus vaccination trials against infection of heterologous strains in mouse models thus far.

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A Field Trial of a Vaccine Prepared From the Volner Strain of Rickettsia Tsutsugamushi

Cited by 22 publications

References 0 publications

Scrub Typhus Vaccine Candidate Kp r56 Induces Humoral and Cellular Immune Responses in Cynomolgus Monkeys

Scrub Typhus Vaccine Candidate Kp r56 Induces Humoral and Cellular Immune Responses in Cynomolgus Monkeys

Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

Immunization with an Autotransporter Protein of Orientia tsutsugamushi Provides Protective Immunity against Scrub Typhus

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