{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T20:02:42Z","timestamp":1778961762557,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI078213"],"award-info":[{"award-number":["AI078213"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 AI057156"],"award-info":[{"award-number":["U54 AI057156"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-07-1-0304"],"award-info":[{"award-number":["W81XWH-07-1-0304"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["DTRA1-CMB-03"],"award-info":[{"award-number":["DTRA1-CMB-03"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Protective immunity against Coxiella burnetii infection is conferred by vaccination with virulent (PI-WCV), but not avirulent (PII-WCV) whole-cell inactivated bacterium. The only well-characterized antigenic difference between virulent and avirulent C. burnetii is they have smooth and rough lipopolysaccharide (LPS), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were vaccinated with PI-WCV and PII-WCV. Humoral and cellular responses were evaluated using protein chip microarrays and ELISpots, respectively. Dendritic cell (DC) maturation after stimulation with PI-WVC and PII-WVC was evaluated using flow cytometry. Vaccine-challenge studies were performed to validate the importance of the receptor CCR7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Other than specific antibody response to PI-LPS, similar antibody profiles were observed but IgG titers were significantly higher after vaccination with PI-WCV. Furthermore, higher frequency of antigen-specific CD4+ T cells was detected in mice immunized with PI-WCV. PI-WCV\u2013stimulated DCs displayed significantly higher levels of CCR7 and migratory ability to secondary lymphoid organs. Challenge-protection studies in wild-type and CCR7-deficient mice confirmed that CCR7 is critical for PI-WCV\u2013induced cellular immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PI-WVC stimulates protective immunity to C. burnetii in mice through stimulation of migratory behavior in DCs for protective cellular immunity. Additionally, the humoral immune response to LPS is an important component of protective immunity.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiz146","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T04:28:14Z","timestamp":1553747294000},"page":"624-634","source":"Crossref","is-referenced-by-count":10,"title":["Chemokine Receptor 7 Is Essential for Coxiella burnetii Whole-Cell Vaccine-Induced Cellular Immunity but Dispensable for Vaccine-Mediated Protective Immunity"],"prefix":"10.1093","volume":"220","author":[{"given":"Chen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin J","family":"van Schaik","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony E","family":"Gregory","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Vigil","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of California, Irvine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip L","family":"Felgner","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of California, Irvine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura R","family":"Hendrix","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Faris","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3896-8581","authenticated-orcid":false,"given":"James E","family":"Samuel","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"2020040120051559000_CIT0001","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrmicro3049","article-title":"Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii","volume":"11","author":"van Schaik","year":"2013","journal-title":"Nat Rev Microbiol"},{"key":"2020040120051559000_CIT0002","first-page":"183","article-title":"Q fever as a biological weapon","volume":"18","author":"Kagawa","year":"2003","journal-title":"Semin Respir Infect"},{"key":"2020040120051559000_CIT0003","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S1473-3099(03)00804-1","article-title":"Q fever: a biological weapon in your backyard","volume":"3","author":"Madariaga","year":"2003","journal-title":"Lancet Infect Dis"},{"key":"2020040120051559000_CIT0004","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1749-6632.1990.tb42203.x","article-title":"The role of lipopolysaccharides in the virulence of Coxiella burnetii.","volume":"590","author":"Hackstadt","year":"1990","journal-title":"Ann N Y Acad Sci"},{"key":"2020040120051559000_CIT0005","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1128\/IAI.48.2.359-365.1985","article-title":"Lipopolysaccharide variation in Coxiella burnetti: intrastrain heterogeneity in structure and antigenicity","volume":"48","author":"Hackstadt","year":"1985","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0006","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/IAI.52.1.337-340.1986","article-title":"Antigenic variation in the phase I lipopolysaccharide of Coxiella burnetii isolates","volume":"52","author":"Hackstadt","year":"1986","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0007","doi-asserted-by":"crossref","first-page":"e1006922","DOI":"10.1371\/journal.ppat.1006922","article-title":"Genetic mechanisms of Coxiella burnetii lipopolysaccharide phase variation","volume":"14","author":"Beare","year":"2018","journal-title":"PLoS Pathog"},{"key":"2020040120051559000_CIT0008","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-94-007-4315-1_4","article-title":"Lipopolysaccharide of Coxiella burnetii","volume-title":"Coxiella burnetii: recent advances and new perspectives in research of the Q fever bacterium,","author":"Narasaki","year":"2012"},{"key":"2020040120051559000_CIT0009","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1128\/IAI.55.5.1144-1150.1987","article-title":"Comparative virulence of intra- and interstrain lipopolysaccharide variants of Coxiella burnetii in the guinea pig model","volume":"55","author":"Moos","year":"1987","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0010","first-page":"265","article-title":"A live vaccine 1\/M-44 against Q-fever for oral use","volume":"12","author":"Genig","year":"1968","journal-title":"J Hyg Epi Microbiol Immun"},{"key":"2020040120051559000_CIT0011","first-page":"389","article-title":"Immunogenicity and reactogenicity of a Q fever chemovaccine in persons professionally exposed to Q fever in Czechoslovakia","volume":"60","author":"Kazar","year":"1982","journal-title":"Bull World Health Organ"},{"key":"2020040120051559000_CIT0012","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1017\/S0950268800059458","article-title":"Vaccine prophylaxis of abattoir-associated Q fever: eight years\u2019 experience in Australian abattoirs","volume":"104","author":"Marmion","year":"1990","journal-title":"Epidemiol Infect"},{"key":"2020040120051559000_CIT0013","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1749-6632.1992.tb19633.x","article-title":"Vaccines against coxiellosis and Q fever. Development of a chloroform:methanol residue subunit of phase I Coxiella burnetii for the immunization of animals","volume":"653","author":"Williams","year":"1992","journal-title":"Ann N Y Acad Sci"},{"key":"2020040120051559000_CIT0014","doi-asserted-by":"crossref","first-page":"8372","DOI":"10.4049\/jimmunol.179.12.8372","article-title":"Mechanisms of vaccine-induced protective immunity against Coxiella burnetii infection in BALB\/c mice","volume":"179","author":"Zhang","year":"2007","journal-title":"J Immunol"},{"key":"2020040120051559000_CIT0015","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4049\/jimmunol.92.3.404","article-title":"The influence of phase on the protective potency of Q fever vaccine","volume":"92","author":"Ormsbee","year":"1964","journal-title":"J Immunol"},{"key":"2020040120051559000_CIT0016","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1128\/CVI.00613-12","article-title":"Long-term immune responses to Coxiella burnetii after vaccination","volume":"20","author":"Kersh","year":"2013","journal-title":"Clin Vaccine Immunol"},{"key":"2020040120051559000_CIT0017","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/milmed\/129.7.591","article-title":"Recurrent reaction at site of Q fever vaccination in a sensitized person","volume":"129","author":"Bell","year":"1964","journal-title":"Mil Med"},{"key":"2020040120051559000_CIT0018","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/S0140-6736(84)91617-9","article-title":"Vaccine prophylaxis of abattoir-associated Q fever","volume":"2","author":"Marmion","year":"1984","journal-title":"Lancet"},{"key":"2020040120051559000_CIT0019","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2249.1993.tb08226.x","article-title":"Variation in interferon-gamma responses to Coxiella burnetii antigens with lymphocytes from vaccinated or naturally infected subjects","volume":"94","author":"Izzo","year":"1993","journal-title":"Clin Exp Immunol"},{"key":"2020040120051559000_CIT0020","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1365-2249.1991.tb05689.x","article-title":"Analysis of the cells involved in the lymphoproliferative response to Coxiella burnetii antigens","volume":"85","author":"Izzo","year":"1991","journal-title":"Clin Exp Immunol"},{"key":"2020040120051559000_CIT0021","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/infdis\/157.4.781","article-title":"Markers of cell-mediated immunity after vaccination with an inactivated, whole-cell Q fever vaccine","volume":"157","author":"Izzo","year":"1988","journal-title":"J Infect Dis"},{"key":"2020040120051559000_CIT0022","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1128\/IAI.16.2.518-521.1977","article-title":"Appearance of cellular and humoral immunity in guinea pigs after infection with Coxiella burnetii administered in small-particle aerosols","volume":"16","author":"Kishimoto","year":"1977","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0023","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1128\/IAI.19.1.194-198.1978","article-title":"Cell-mediated immune responses of guinea pigs to an inactivated phase I Coxiella burnetii vaccine","volume":"19","author":"Kishimoto","year":"1978","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0024","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1128\/IAI.31.2.641-645.1981","article-title":"Role of antibody in Coxiella burnetii infection","volume":"31","author":"Humphres","year":"1981","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0025","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1099\/mic.0.043513-0","article-title":"Immunoreactive Coxiella burnetii Nine Mile proteins separated by 2D electrophoresis and identified by tandem mass spectrometry","volume":"157","author":"Deringer","year":"2011","journal-title":"Microbiology"},{"key":"2020040120051559000_CIT0026","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fcimb.2017.00025","article-title":"The SCID mouse model for identifying virulence determinants in Coxiella burnetii","volume":"7","author":"van Schaik","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"2020040120051559000_CIT0027","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1128\/CVI.00300-08","article-title":"Candidate antigens for Q fever serodiagnosis revealed by immunoscreening of a Coxiella burnetii protein microarray","volume":"15","author":"Beare","year":"2008","journal-title":"Clin Vaccine Immunol"},{"key":"2020040120051559000_CIT0028","doi-asserted-by":"crossref","first-page":"M110.006304","DOI":"10.1074\/mcp.M110.006304","article-title":"Profiling the humoral immune response of acute and chronic Q fever by protein microarray","volume":"10","author":"Vigil","year":"2011","journal-title":"Mol Cell Proteomics"},{"key":"2020040120051559000_CIT0029","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1002\/pmic.201000064","article-title":"Genome-wide profiling of humoral immune response to Coxiella burnetii infection by protein microarray","volume":"10","author":"Vigil","year":"2010","journal-title":"Proteomics"},{"key":"2020040120051559000_CIT0030","first-page":"224","article-title":"Basic structural features of a lipopolysaccharide from the Coxiella burnetii strain Nine Mile in the virulent phase I","volume":"36","author":"Toman","year":"1992","journal-title":"Acta Virol"},{"key":"2020040120051559000_CIT0031","doi-asserted-by":"publisher","DOI":"10.3791\/52739","article-title":"Mouse Naive CD4+ T cell isolation and in vitro differentiation into T cell subsets","volume":"98","author":"Flaherty","year":"2015","journal-title":"J Vis Exp"},{"key":"2020040120051559000_CIT0032","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0022-1759(98)00204-X","article-title":"An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow","volume":"223","author":"Lutz","year":"1999","journal-title":"J Immunol Methods"},{"key":"2020040120051559000_CIT0033","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.4049\/jimmunol.164.6.2937","article-title":"Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model","volume":"164","author":"Lambrecht","year":"2000","journal-title":"J Immunol"},{"key":"2020040120051559000_CIT0034","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1128\/IAI.01767-06","article-title":"T cells are essential for bacterial clearance, and gamma interferon, tumor necrosis factor alpha, and B cells are crucial for disease development in Coxiella burnetii infection in mice","volume":"75","author":"Andoh","year":"2007","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0035","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1128\/IAI.00101-10","article-title":"Role of CD4+ and CD8+ T cells in clearance of primary pulmonary infection with Coxiella burnetii","volume":"78","author":"Read","year":"2010","journal-title":"Infect Immun"},{"key":"2020040120051559000_CIT0036","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.4049\/jimmunol.162.5.2472","article-title":"Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes","volume":"162","author":"Saeki","year":"1999","journal-title":"J Immunol"},{"key":"2020040120051559000_CIT0037","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.4049\/jimmunol.172.6.3695","article-title":"Lipopolysaccharide from Coxiella burnetii is involved in bacterial phagocytosis, filamentous actin reorganization, and inflammatory responses through Toll-like receptor 4","volume":"172","author":"Honstettre","year":"2004","journal-title":"J Immunol"},{"key":"2020040120051559000_CIT0038","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.chom.2012.10.015","article-title":"Impaired stimulation of p38\u03b1-MAPK\/Vps41-HOPS by LPS from pathogenic Coxiella burnetii prevents trafficking to microbicidal phagolysosomes","volume":"12","author":"Barry","year":"2012","journal-title":"Cell Host Microbe"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiz146\/28900529\/jiz146.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/220\/4\/624\/28955722\/jiz146.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/220\/4\/624\/28955722\/jiz146.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T23:18:37Z","timestamp":1694733517000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/220\/4\/624\/5425888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,2]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4,2]]},"published-print":{"date-parts":[[2019,7,19]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiz146","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8,15]]},"published":{"date-parts":[[2019,4,2]]}}}