ArticleJournal of immunology (Baltimore, Md. : 1950)2015
A nonhuman primate scrub typhus model: protective immune responses induced by pKarp47 DNA vaccination in cynomolgus macaques.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Scrub Typhus Presenting with Isolated Xerostomia.The American journal of tropical medicine and hygiene · 2026Article
- Neglected rickettsial diseases in Southeast Asia: Twenty-five years of progress in surveillance, diagnostics, and clinical research.PLoS neglected tropical diseases · 2026Review
- A humanized IFN-γ mouse model reveals skin eschar formation, enhanced susceptibility and scrub typhus pathogenesis.PLoS pathogens · 2026Article
- Advancing the diagnosis of scrub typhus with targeted next-generation sequencing.Frontiers in microbiology · 2026Article
- Patient-centric analysis of Orientia tsutsugamushi spatial diversity patterns across Hainan Island, China.PLoS neglected tropical diseases · 2025Article
- Lack of the IFN-γ signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions.PLoS pathogens · 2024Article
- Diagnostic accuracy of DPP Fever Panel II Asia tests for tropical fever diagnosis.PLoS neglected tropical diseases · 2024Article
- A proof of concept for a targeted enrichment approach to the simultaneous detection and characterization of rickettsial pathogens from clinical specimens.Frontiers in microbiology · 2024Article
- A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus.PLoS neglected tropical diseases · 2023Article
- A scrub typhus vaccine presents a challenging unmet need.NPJ vaccines · 2023Review
- A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.PLoS neglected tropical diseases · 2022Article
- Simple clinical and laboratory predictors to improve empirical treatment strategies in areas of high scrub typhus and dengue endemicity, central Vietnam.PLoS neglected tropical diseases · 2022Article
- Special Issue "The Past and Present Threat of Rickettsial Diseases".Tropical medicine and infectious disease · 2020Article
- A Brief History of the Major Rickettsioses in the Asia-Australia-Pacific Region: A Capstone Review for the Special Issue ofTropical medicine and infectious disease · 2020Review
- Clinical Characteristics and Outcome of Children Hospitalized With Scrub Typhus in an Area of Endemicity.Journal of the Pediatric Infectious Diseases Society · 2020Article
- The estimated burden of scrub typhus in Thailand from national surveillance data (2003-2018).PLoS neglected tropical diseases · 2020Article
- Temporal analysis of mRNA expression profiles in Orientia infected C3HeB/FeJ mouse.BMC microbiology · 2020Article
- Biosafety and biosecurity requirements for Orientia spp. diagnosis and research: recommendations for risk-based biocontainment, work practices and the case for reclassification to risk group 2.BMC infectious diseases · 2019Article
- Determination of Optimal Diagnostic Cut-Offs for the Naval Medical Research Center Scrub Typhus IgM ELISA in Chiang Rai, Thailand.The American journal of tropical medicine and hygiene · 2019Article
- Immunization with a recombinant antigen composed of conserved blocks from TSA56 provides broad genotype protection against scrub typhus.Emerging microbes & infections · 2019Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly increased O. tsutsugamushi-specific, IFN-γ-producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p ≤ 0.01), delayed bacteremia onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p < 0.03) than controls. This study demonstrates a vaccine-induced immune response capable of conferring sterile immunity against high-dose homologous ID challenge of O. tsutsugamushi in a nonhuman primate model, and it provides insight into cell-mediated immune control of O. tsutsugamushi and dissemination dynamics, highlights the importance of bacteremia indices for evaluation of both natural and vaccine-induced immune responses, and importantly, to our knowledge, has determined the first phenotypic correlates of immune protection in scrub typhus. We conclude that this model is suitable for detailed investigations into vaccine-induced immune responses and correlates of immunity for scrub typhus.
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