{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:02:28Z","timestamp":1783702948103,"version":"3.55.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":3687,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2013specific, IFN-\u03b3\u2013producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p \u2264 0.01), delayed bacteremia onset (p &amp;lt; 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p &amp;lt; 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1402244","type":"journal-article","created":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T05:11:30Z","timestamp":1421730690000},"page":"1702-1716","source":"Crossref","is-referenced-by-count":37,"title":["A Nonhuman Primate Scrub Typhus Model: Protective Immune Responses Induced by pKarp47 DNA Vaccination in Cynomolgus Macaques"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-5987","authenticated-orcid":false,"given":"Daniel H","family":"Paris","sequence":"first","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400 ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford , Oxford, OX3 7FZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchismita","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Viral and Rickettsial Diseases Department, Naval Medical Research Center , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Jiang","sequence":"additional","affiliation":[{"name":"Viral and Rickettsial Diseases Department, Naval Medical Research Center , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pruksa","family":"Nawtaisong","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Entomology, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esterlina","family":"Tan","sequence":"additional","affiliation":[{"name":"Leonard Wood Memorial Institute , Cebu 6000 ,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Dela Cruz","sequence":"additional","affiliation":[{"name":"Leonard Wood Memorial Institute , Cebu 6000 ,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Burgos","sequence":"additional","affiliation":[{"name":"Leonard Wood Memorial Institute , Cebu 6000 ,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Abalos","sequence":"additional","affiliation":[{"name":"Leonard Wood Memorial Institute , Cebu 6000 ,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart D","family":"Blacksell","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400 ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford , Oxford, OX3 7FZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lombardini","sequence":"additional","affiliation":[{"name":"Veterinary Medicine Department, Armed Forces Medical Research Institute of Science , Thanon Yothi, 10400 Bangkok"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth D","family":"Turner","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400 ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford , Oxford, OX3 7FZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P J","family":"Day","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400 ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford , Oxford, OX3 7FZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen L","family":"Richards","sequence":"additional","affiliation":[{"name":"Viral and Rickettsial Diseases Department, Naval Medical Research Center , Silver Spring, MD 20910"},{"name":"Preventive Medicine and Biometrics Department, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,15]]},"reference":[{"key":"2025030705053399900_r1","doi-asserted-by":"crossref","first-page":"S145","DOI":"10.1086\/339908","article-title":"The past and present threat of rickettsial diseases to military medicine and international public health","volume":"34","author":"Kelly","year":"2002","journal-title":"Clin. 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Lett."},{"key":"2025030705053399900_r32","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4269\/ajtmh.2003.69.60","article-title":"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","volume":"69","author":"Jiang","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"2025030705053399900_r33","doi-asserted-by":"crossref","first-page":"11634","DOI":"10.1128\/JVI.00996-07","article-title":"A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques","volume":"81","author":"Chen","year":"2007","journal-title":"J. Virol."},{"key":"2025030705053399900_r34","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1743-422X-2-2","article-title":"Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons","volume":"2","author":"Bruce","year":"2005","journal-title":"Virol. J."},{"key":"2025030705053399900_r35","first-page":"603","article-title":"A comparative study of the pathology of scrub typhus (Tsutsugamushi disease) and other rickettsial diseases","volume":"21","author":"Allen","year":"1945","journal-title":"Am. J. Pathol."},{"key":"2025030705053399900_r36","first-page":"847","article-title":"Immunity in scrub typhus: resistance to induced reinfection","volume":"50","author":"Smadel","year":"1950","journal-title":"AMA Arch. Pathol."},{"key":"2025030705053399900_r37","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3201\/eid1202.050900","article-title":"Rickettsial infections and fever, Vientiane, Laos","volume":"12","author":"Phongmany","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"2025030705053399900_r38","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1097\/INF.0b013e3181af8287","article-title":"Characteristics of pediatric scrub typhus in a new endemic region of northern China","volume":"28","author":"Liu","year":"2009","journal-title":"Pediatr. Infect. Dis. J."},{"key":"2025030705053399900_r39","doi-asserted-by":"crossref","first-page":"345","DOI":"10.7883\/yoken1952.32.345","article-title":"Comparison of experimental Rickettsia tsutsugamushi infections in silvered leaf (Presbytis cristatus) and cynomolgus (Macaca fascicularis) monkeys","volume":"32","author":"Shirai","year":"1979","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"2025030705053399900_r40","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1574-695X.2007.00375.x","article-title":"Genetic typing of the 56-kDa type-specific antigen gene of contemporary Orientia tsutsugamushi isolates causing human scrub typhus at two sites in north-eastern and western Thailand","volume":"52","author":"Blacksell","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"2025030705053399900_r41","doi-asserted-by":"crossref","first-page":"S203","DOI":"10.1086\/596576","article-title":"Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi","volume":"48","author":"Kelly","year":"2009","journal-title":"Clin. Infect. 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Sci."},{"key":"2025030705053399900_r48","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature10851","article-title":"Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity","volume":"483","author":"Jiang","year":"2012","journal-title":"Nature"},{"key":"2025030705053399900_r49","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1128\/JVI.03361-12","article-title":"Venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus","volume":"87","author":"Herbert","year":"2013","journal-title":"J. Virol."},{"key":"2025030705053399900_r50","first-page":"262","article-title":"Vaccines against asexual stage malaria parasites","volume":"80","author":"Kumar","year":"2002","journal-title":"Chem. Immunol."},{"key":"2025030705053399900_r51","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/cgt.2013.65","article-title":"DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques","volume":"20","author":"Obeng-Adjei","year":"2013","journal-title":"Cancer Gene Ther."},{"key":"2025030705053399900_r52","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1128\/iai.42.1.341-349.1983","article-title":"Effect of immune serum on infectivity of Rickettsia tsutsugamushi","volume":"42","author":"Hanson","year":"1983","journal-title":"Infect. Immun."},{"key":"2025030705053399900_r53","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1128\/iai.39.2.928-938.1983","article-title":"Effect of antibody on entry of Rickettsia tsutsugamushi into polymorphonuclear leukocyte cytoplasm","volume":"39","author":"Rikihisa","year":"1983","journal-title":"Infect. 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