{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:31:48Z","timestamp":1788831108125,"version":"build-2803163510"},"reference-count":193,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii that presents significant challenges for global public health control. Current prevention relies primarily on the whole-cell vaccine \u201cQ-VAX\u201d, which despite its effectiveness, faces important limitations including pre-screening requirements and reactogenicity issues in previously sensitized individuals. This comprehensive review examines the complex interplay between pathogen characteristics, host immune responses, and vaccine development strategies. We analyze recent advances in understanding C. burnetii\u2019s molecular pathogenesis and host\u2013pathogen interactions that have informed vaccine design. The evolution of vaccine approaches is evaluated, from traditional whole-cell preparations to modern subunit, DNA, and multi-epitope designs. Particular attention is given to innovative technologies, including reverse vaccinology and immunoinformatics, that have enabled the identification of novel antigenic targets. Recent clinical data demonstrating the safety and immunogenicity of next-generation vaccine candidates are presented, alongside manufacturing and implementation considerations. While significant progress has been made in overcoming the limitations of first-generation vaccines, challenges remain in optimizing immunogenicity while ensuring safety across diverse populations. This review provides a critical analysis of current evidence and future directions in Q fever vaccine development, highlighting promising strategies for achieving more effective and broadly applicable vaccines.<\/jats:p>","DOI":"10.3390\/vaccines13020151","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Q Fever Vaccines: Unveiling the Historical Journey and Contemporary Innovations in Vaccine Development"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2976-9460","authenticated-orcid":false,"given":"Magdalini","family":"Christodoulou","sequence":"first","affiliation":[{"name":"Public Health & Adults Immunization Laboratory, Department of Nursing, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6123-559X","authenticated-orcid":false,"given":"Dimitrios","family":"Papagiannis","sequence":"additional","affiliation":[{"name":"Public Health & Adults Immunization Laboratory, Department of Nursing, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1128\/CMR.00045-16","article-title":"From Q Fever to Coxiella burnetii Infection: A Paradigm Change","volume":"30","author":"Eldin","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.jinf.2015.04.024","article-title":"Recent advances in the study of Q fever epidemiology, diagnosis and management","volume":"71","author":"Million","year":"2015","journal-title":"J. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chmel, H., Bendinelli, M., and Friedman, H. (1994). Coxiella burnetii and Q Fever. Pulmonary Infections and Immunity, Springer.","DOI":"10.1007\/978-1-4899-1063-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5694\/j.1326-5377.1938.tb110236.x","article-title":"The Rickettsia of \u201cQ\u201d Fever: Further Experimental Studies","volume":"1","author":"Burnet","year":"1938","journal-title":"Med. J. Aust."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lorenzo-Morales, J. (2012). Coxiella burnetii. Zoonosis, InTech. Available online: http:\/\/www.intechopen.com\/books\/zoonosis\/coxiella-burnetii.","DOI":"10.5772\/2125"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"K\u00f6rner, S., Makert, G.R., Ulbert, S., Pfeffer, M., and Mertens-Scholz, K. (2021). The Prevalence of Coxiella burnetii in Hard Ticks in Europe and Their Role in Q Fever Transmission Revisited\u2014A Systematic Review. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.655715"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1136\/bmj.1.5641.443","article-title":"Lysosomes and menstruation","volume":"1","author":"Wood","year":"1969","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bauer, B.U., Knittler, M.R., Andrack, J., Berens, C., Campe, A., Christiansen, B., Fasemore, A.M., Fischer, S.F., Ganter, M., and K\u00f6rner, S. (2023). Interdisciplinary studies on Coxiella burnetii: From molecular to cellular, to host, to one health research. Int. J. Med. Microbiol., 313.","DOI":"10.1016\/j.ijmm.2023.151590"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1196\/annals.1355.018","article-title":"Coxiella burnetii Infection","volume":"1063","author":"Kazar","year":"2005","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1177\/153567600601100106","article-title":"The Infectious Dose of Coxiella burnetii (Q Fever)","volume":"11","author":"Jones","year":"2006","journal-title":"Appl. Biosaf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1016\/j.vaccine.2020.08.006","article-title":"Q fever vaccine efficacy and occupational exposure risk in Queensland, Australia: A retrospective cohort study","volume":"38","author":"Woldeyohannes","year":"2020","journal-title":"Vaccine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"901","DOI":"10.13075\/ijomeh.1896.00448","article-title":"Seroprevalence and occupational risk survey for Coxiella burnetii among exposed workers in Sicily, Southern Italy","volume":"28","author":"Fenga","year":"2015","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4488","DOI":"10.4049\/jimmunol.169.8.4488","article-title":"Coxiella burnetii Survival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-\u03b3 Mediates its Restoration and Bacterial Killing","volume":"169","author":"Ghigo","year":"2002","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1128\/IAI.00594-07","article-title":"Coxiella burnetii Inhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages","volume":"75","author":"Voth","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Coiffard, B., Soubeyran, P., and Ghigo, E. (2015). Editorial: Manipulation of the cellular microbicidal response and endocytic dynamic by pathogens membrane factors. Front. Cell Infect. Microbiol., 5, Available online: http:\/\/www.frontiersin.org\/Cellular_and_Infection_Microbiology\/10.3389\/fcimb.2015.00042\/full.","DOI":"10.3389\/fcimb.2015.00042"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1128\/IAI.69.8.4874-4883.2001","article-title":"Characterization of a Stress-Induced Alternate Sigma Factor, RpoS, of Coxiella burnetii and Its Expression during the Development Cycle","volume":"69","author":"Seshadri","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1749-6632.2003.tb07440.x","article-title":"Molecular Pathogenesis of Coxiella burnetii in a Genomics Era","volume":"990","author":"Samuel","year":"2003","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_18","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 Proteom."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiong, X., Wang, X., Wen, B., Graves, S., and Stenos, J. (2012). Potential serodiagnostic markers for Q fever identified in Coxiella burnetiid by immunoproteomic and protein microarray approaches. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-35"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Toman, R., Heinzen, R.A., Samuel, J.E., and Mege, J.L. (2012). Antigenic Analysis for Vaccines and Diagnostics. Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium, Springer.","DOI":"10.1007\/978-94-007-4315-1"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Vergunst, A.C., and O\u2019Callaghan, D. (2014). Gene Inactivation in Coxiella burnetii. Host-Bacteria Interactions, Springer.","DOI":"10.1007\/978-1-4939-1261-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1128\/AEM.02826-10","article-title":"Isolation from Animal Tissue and Genetic Transformation of Coxiella burnetii Are Facilitated by an Improved Axenic Growth Medium","volume":"77","author":"Omsland","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1574-695X.2011.00876.x","article-title":"The 2007\u20132010 Q fever epidemic in the Netherlands: Characteristics of notified acute Q fever patients and the association with dairy goat farming","volume":"64","author":"Dijkstra","year":"2012","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Roest, H.J., Van Gelderen, B., Dinkla, A., Frangoulidis, D., Van Zijderveld, F., Rebel, J., and van Keulen, L. (2012). Q Fever in Pregnant Goats: Pathogenesis and Excretion of Coxiella burnetii. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048949"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1017\/S0950268812001203","article-title":"Screening for Coxiella burnetii seroprevalence in chronic Q fever high-risk groups reveals the magnitude of the Dutch Q fever outbreak","volume":"141","author":"Kampschreur","year":"2013","journal-title":"Epidemiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s12026-008-8059-4","article-title":"Adaptive immunity to the obligate intracellular pathogen Coxiella burnetii","volume":"43","author":"Shannon","year":"2009","journal-title":"Immunol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.5694\/j.1326-5377.2007.tb00853.x","article-title":"Q fever: The long journey to control by vaccination","volume":"186","author":"Marmion","year":"2007","journal-title":"Med. J. Aust."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1469-0691.2008.02206.x","article-title":"A systematic approach to evaluate humoral and cellular immune responses to Coxiella burnetii immunoreactive antigens","volume":"15","author":"Chen","year":"2009","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_29","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":"ref_30","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.1016\/j.vaccine.2017.10.088","article-title":"Q-Vax Q fever vaccine failures, Victoria, Australia 1994\u20132013","volume":"35","author":"Bond","year":"2017","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.vaccine.2010.11.008","article-title":"Effectiveness of the Q fever vaccine: A meta-analysis","volume":"29","author":"Gefenaite","year":"2011","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1093\/cid\/cit129","article-title":"Specific interferon \u03b3 detection for the diagnosis of previous Q fever","volume":"56","author":"Schoffelen","year":"2013","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, C., Dow, C., Wang, P., Sidney, J., Read, A., Harmsen, A., Samuel, J.E., and Peters, B. (2011). Identification of CD4+ T Cell Epitopes in C. burnetii Antigens Targeted by Antibody Responses. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017712"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Xiong, X., Qi, Y., Jiao, J., Gong, W., Duan, C., and Wen, B. (2014). Exploratory Study on Th1 Epitope-Induced Protective Immunity against Coxiella burnetii Infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087206"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1196\/annals.1355.021","article-title":"Protective Immunity against Q Fever Induced with a Recombinant P1 Antigen Fused with HspB of Coxiella burnetii","volume":"1063","author":"Li","year":"2005","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bach, E., Fitzgerald, S.F., Williams-MacDonald, S.E., Mitchell, M., Golde, W.T., Longbottom, D., Nisbet, A.J., Dinkla, A., Sullivan, E., and Pinapati, R.S. (2023). Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1257722"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Arricau-Bouvery, N., Hauck, Y., Bejaoui, A., Frangoulidis, D., Bodier, C.C., Souriau, A., Meyer, H., Neubauer, H., Rodolakis, A., and Vergnaud, G. (2006). Molecular characterization of Coxiella burnetii isolates by infrequent restriction site-PCR and MLVA typing. BMC Microbiol., 6.","DOI":"10.1186\/1471-2180-6-38"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Porter, S.R., Czaplicki, G., Mainil, J., Guatt\u00e9o, R., and Saegerman, C. (2011). Q Fever: Current state of knowledge and perspectives of research of a neglected zoonosis. Int. J. Microbiol., 2011.","DOI":"10.1155\/2011\/248418"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.pt.2018.09.008","article-title":"The Importance of Revisiting Legionellales Diversity","volume":"34","author":"Duron","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Smith, C.B., Evavold, C., and Kersh, G.J. (2019). The Effect of pH on Antibiotic Efficacy against Coxiella burnetii in Axenic Media. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-54556-6"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Vallejo Esquerra, E., Yang, H., Sanchez, S.E., and Omsland, A. (2017). Physicochemical and Nutritional Requirements for Axenic Replication Suggest Physiological Basis for Coxiella burnetii Niche Restriction. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00190"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-3-319-75241-9_10","article-title":"Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis","volume":"Volume 413","author":"Backert","year":"2017","journal-title":"Type IV Secretion in Gram-Negative and Gram-Positive Bacteria"},{"key":"ref_43","first-page":"231","article-title":"Developmental Biology of Coxiella burnetii","volume":"Volume 984","author":"Toman","year":"2012","journal-title":"Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e00410","DOI":"10.1128\/iai.00410-22","article-title":"Developmental Transitions Coordinate Assembly of the Coxiella burnetii Dot\/Icm Type IV Secretion System","volume":"90","author":"Park","year":"2022","journal-title":"Infect. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e221769","DOI":"10.3201\/eid2907.221769","article-title":"Epidemiology of Pathogens Listed as Potential Bioterrorism Agents, the Netherlands, 2009\u20132019","volume":"29","author":"Broertjes","year":"2023","journal-title":"Emerg Infect Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1128\/AEM.00042-10","article-title":"Presence of Coxiella burnetii DNA in the Environment of the United States, 2006 to 2008","volume":"76","author":"Kersh","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_47","first-page":"829","article-title":"The geographical distribution of Q fever","volume":"13","author":"Kaplan","year":"1955","journal-title":"Bull. World Health Organ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.1128\/JB.186.21.7344-7352.2004","article-title":"Temporal Analysis of Coxiella burnetii Morphological Differentiation","volume":"186","author":"Coleman","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sandoz, K.M., Popham, D.L., Beare, P.A., Sturdevant, D.E., Hansen, B., Nair, V., and Heinzen, R.A. (2016). Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell Wall Remodeling in the Small Cell Variant Developmental Form. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149957"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lightfoot, N.F., and Lloyd, G. (2010). Coxiella burnetii. Topley & Wilson\u2019s Microbiology and Microbial Infections, John Wiley & Sons, Ltd.","DOI":"10.1002\/9780470688618.taw0081"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1128\/jb.160.3.989-993.1984","article-title":"Sensitivity of Coxiella burnetii peptidoglycan to lysozyme hydrolysis and correlation of sacculus rigidity with peptidoglycan-associated proteins","volume":"160","author":"Amano","year":"1984","journal-title":"J. Bacteriol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1128\/jb.147.3.1063-1076.1981","article-title":"Developmental cycle of Coxiella burnetii: Structure and morphogenesis of vegetative and sporogenic differentiations","volume":"147","author":"McCaul","year":"1981","journal-title":"J. Bacteriol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000357107","article-title":"Coxiella burnetii\u2014Pathogenic Agent of Q (Query) Fever","volume":"41","author":"Bauerfeind","year":"2014","journal-title":"Transfus. Med. Hemotherapy"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Morigen, G.M., and Xie, J. (2021). Editorial: Bacterial Transcription Factors and the Cell Cycle. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.821394"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1084\/jem.192.9.1261","article-title":"Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles","volume":"192","author":"Swanson","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_56","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. NY Acad. Sci."},{"key":"ref_57","first-page":"65","article-title":"Lipopolysaccharide of Coxiella burnetii","volume":"Volume 984","author":"Toman","year":"2012","journal-title":"Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1128\/iai.56.1.40-44.1988","article-title":"Lipopolysaccharide phase variation determines the complement-mediated serum susceptibility of Coxiella burnetii","volume":"56","author":"Vishwanath","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"54405","DOI":"10.1074\/jbc.M410340200","article-title":"Stimulation of Toll-like Receptor 2 by Coxiella burnetii Is Required for Macrophage Production of Pro-inflammatory Cytokines and Resistance to Infection","volume":"279","author":"Zamboni","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wang, T., Yu, Y., Liang, X., Luo, S., He, Z., Sun, Z., Jiang, Y., Omsland, A., Zhou, P., and Song, L. (2018). Lipid A Has Significance for Optimal Growth of Coxiella burnetii in Macrophage-Like THP-1 Cells and to a Lesser Extent in Axenic Media and Non-phagocytic Cells. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00192"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6741","DOI":"10.1128\/IAI.70.12.6741-6750.2002","article-title":"Cloning and Porin Activity of the Major Outer Membrane Protein P1 from Coxiella burnetii","volume":"70","author":"Varghees","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4149\/av_2010_03_173","article-title":"Characterization of antigens for Q fever serodiagnostics","volume":"54","author":"Kowalczewska","year":"2010","journal-title":"Acta Virol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Carey, K.L., Newton, H.J., L\u00fchrmann, A., and Roy, C.R. (2011). The Coxiella burnetii Dot\/Icm System Delivers a Unique Repertoire of Type IV Effectors into Host Cells and Is Required for Intracellular Replication. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002056"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1128\/IAI.71.7.3714-3723.2003","article-title":"Functional Similarities between the icm\/dot Pathogenesis Systems of Coxiella burnetii and Legionella pneumophila","volume":"71","author":"Zusman","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Nagai, H., and Kubori, T. (2011). Type IVB Secretion Systems of Legionella and Other Gram-Negative Bacteria. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00136"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1111\/j.1462-5822.2008.01187.x","article-title":"Type IV secretion systems: Tools of bacterial horizontal gene transfer and virulence","volume":"10","author":"Juhas","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"21755","DOI":"10.1073\/pnas.1010485107","article-title":"Large-scale identification and translocation of type IV secretion substrates by Coxiella burnetii","volume":"107","author":"Chen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Sch\u00e4fer, W., Eckart, R.A., Schmid, B., Cagk\u00f6yl\u00fc, H., Hof, K., Muller, Y.A., and L\u00fchrmann, A. (2017). Nuclear trafficking of the anti-apoptotic Coxiella burnetii effector protein AnkG requires binding to p32 and Importin-\u03b11: AnkG trafficking into the nucleus. Cell Microbiol., 19.","DOI":"10.1111\/cmi.12634"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1128\/IAI.01204-13","article-title":"Antiapoptotic Activity of Coxiella burnetii Effector Protein AnkG Is Controlled by p32-Dependent Trafficking","volume":"82","author":"Eckart","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1128\/IAI.02763-14","article-title":"Coxiella burnetii Effector Proteins That Localize to the Parasitophorous Vacuole Membrane Promote Intracellular Replication","volume":"83","author":"Larson","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"E3260","DOI":"10.1073\/pnas.1522811113","article-title":"Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development","volume":"113","author":"Martinez","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Swart, A.L., Gomez-Valero, L., Buchrieser, C., and Hilbi, H. (2020). Evolution and function of bacterial RCC1 repeat effectors. Cell Microbiol., 22.","DOI":"10.1111\/cmi.13246"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13708","DOI":"10.1073\/pnas.1914892117","article-title":"Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein","volume":"117","author":"Burette","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Abou Abdallah, R., Million, M., Delerce, J., Anani, H., Diop, A., Caputo, A., Zgheib, R., Rousset, E., Boumedine, K.S., and Raoult, D. (2022). Pangenomic analysis of Coxiella burnetii unveils new traits in genome architecture. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1022356"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1128\/JB.188.7.2309-2324.2006","article-title":"Genetic Diversity of the Q Fever Agent, Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons","volume":"188","author":"Beare","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Long, C. (2021). Q Fever Vaccine Development: Current Strategies and Future Considerations. Pathogens, 10.","DOI":"10.3390\/pathogens10101223"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/cmi.12066","article-title":"The Coxiella burnetii type IV secretion system substrate CaeB inhibits intrinsic apoptosis at the mitochondrial level: Coxiella burnetii anti-apoptotic effector proteins","volume":"15","author":"Klingenbeck","year":"2013","journal-title":"Cell Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1111\/j.1365-2958.2007.05604.x","article-title":"The response regulator PmrA is a major regulator of the icm \/ dot type IV secretion system in Legionella pneumophila and Coxiella burnetii","volume":"63","author":"Zusman","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Moses, A.S., Millar, J.A., Bonazzi, M., Beare, P.A., and Raghavan, R. (2017). Horizontally Acquired Biosynthesis Genes Boost Coxiella burnetii\u2019s Physiology. Front. Cell Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00174"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1042\/BCJ20190504","article-title":"Coxiella burnetii utilizes both glutamate and glucose during infection with glucose uptake mediated by multiple transporters","volume":"476","author":"Kuba","year":"2019","journal-title":"Biochem. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.micinf.2019.09.001","article-title":"Coxiella burnetii: International pathogen of mystery","volume":"22","author":"Dragan","year":"2020","journal-title":"Microbes Infect."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Samanta, D., Clemente, T.M., Schuler, B.E., and Gilk, S.D. (2019). Coxiella burnetii Type 4B Secretion System-dependent manipulation of endolysosomal maturation is required for bacterial growth. PLoS Pathog., 15.","DOI":"10.1101\/645382"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/j.1462-5822.2006.00838.x","article-title":"The autophagic pathway is actively modulated by phase II Coxiella burnetii to efficiently replicate in the host cell","volume":"9","author":"Romano","year":"2007","journal-title":"Cell Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Newton, H.J., Kohler, L.J., McDonough, J.A., Temoche-Diaz, M., Crabill, E., Hartland, E.L., and Roy, C.R. (2014). A Screen of Coxiella burnetii Mutants Reveals Important Roles for Dot\/Icm Effectors and Host Autophagy in Vacuole Biogenesis. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004286"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.micinf.2015.08.006","article-title":"Biogenesis of the lysosome-derived vacuole containing Coxiella burnetii","volume":"17","author":"Kohler","year":"2015","journal-title":"Microbes Infect."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Latomanski, E.A., Newton, P., Khoo, C.A., and Newton, H.J. (2016). The Effector Cig57 Hijacks FCHO-Mediated Vesicular Trafficking to Facilitate Intracellular Replication of Coxiella burnetii. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1006101"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1128\/IAI.01236-13","article-title":"Coxiella burnetii Type IV Secretion-Dependent Recruitment of Macrophage Autophagosomes","volume":"82","author":"Winchell","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1042\/BST20120167","article-title":"The role of Rab GTPases in the transport of vacuoles containing Legionella pneumophila and Coxiella burnetii","volume":"40","author":"Hardiman","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1128\/IAI.70.10.5816-5821.2002","article-title":"Coxiella burnetii Localizes in a Rab7-Labeled Compartment with Autophagic Characteristics","volume":"70","author":"Gutierrez","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1128\/IAI.00688-10","article-title":"The Early Secretory Pathway Contributes to the Growth of the Coxiella -Replicative Niche","volume":"79","author":"Campoy","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.2217\/fmb.11.116","article-title":"Genetics of Coxiella burnetii: On the Path of Specialization","volume":"6","author":"Minnick","year":"2011","journal-title":"Future Microbiol."},{"key":"ref_92","first-page":"39","article-title":"Defense Mechanisms Against Oxidative Stress in Coxiella burnetii: Adaptation to a Unique Intracellular Niche","volume":"Volume 984","author":"Toman","year":"2012","journal-title":"Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Thomas, D.R., Newton, P., Lau, N., and Newton, H.J. (2020). Interfering with Autophagy: The Opposing Strategies Deployed by Legionella pneumophila and Coxiella burnetii Effector Proteins. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.599762"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e00016","DOI":"10.1128\/iai.00016-22","article-title":"Coxiella burnetii Plasmid Effector B Promotes LC3-II Accumulation and Contributes To Bacterial Virulence in a SCID Mouse Model","volume":"90","author":"Fu","year":"2022","journal-title":"Infect. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1080\/15548627.2020.1728098","article-title":"Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence","volume":"17","author":"Siadous","year":"2021","journal-title":"Autophagy"},{"key":"ref_96","first-page":"273","article-title":"Role of Innate and Adaptive Immunity in the Control of Q Fever","volume":"Volume 984","author":"Toman","year":"2012","journal-title":"Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium"},{"key":"ref_97","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":"ref_98","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/eji.200738067","article-title":"Coxiella burnetii, the agent of Q fever, stimulates an atypical M2 activation program in human macrophages","volume":"38","author":"Benoit","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1111\/cmi.12096","article-title":"Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages: Coxiella infection of alveolar macrophages","volume":"15","author":"Graham","year":"2013","journal-title":"Cell Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Meghari, S., Bechah, Y., Capo, C., Lepidi, H., Raoult, D., Murray, P.J., and Mege, J.-L. (2008). Persistent Coxiella burnetii Infection in Mice Overexpressing IL-10: An Efficient Model for Chronic Q Fever Pathogenesis. PLoS Pathog, 4.","DOI":"10.1371\/journal.ppat.0040023"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1093\/infdis\/jiu526","article-title":"Recognition of Coxiella burnetii by Toll-like Receptors and Nucleotide-Binding Oligomerization Domain-like Receptors","volume":"211","author":"Ammerdorffer","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_102","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":"ref_103","doi-asserted-by":"crossref","unstructured":"Gilk, S.D., Cockrell, D.C., Luterbach, C., Hansen, B., Knodler, L.A., Ibarra, J.A., Steele-Mortimer, O., and Heinzen, R.A. (2013). Bacterial Colonization of Host Cells in the Absence of Cholesterol. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003107"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1574-695X.2011.00890.x","article-title":"Developing a new clinical tool for diagnosing chronic Q fever: The Coxiella ELISPOT: Table 1","volume":"64","author":"Limonard","year":"2012","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1128\/JCM.41.5.1869-1874.2003","article-title":"Evaluation of Coxiella burnetii Antibiotic Susceptibilities by Real-Time PCR Assay","volume":"41","author":"Brennan","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_106","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":"ref_107","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1128\/jb.110.1.368-377.1972","article-title":"Isolation and Characterization of Two Cell Types of Coxiella burneti Phase I","volume":"110","author":"Wiebe","year":"1972","journal-title":"J. Bacteriol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1128\/iai.38.1.53-57.1982","article-title":"Different sugar compositions of lipopolysaccharides isolated from phase I and pure phase II cells of Coxiella burnetii","volume":"38","author":"Schramek","year":"1982","journal-title":"Infect. Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1128\/iai.41.3.1089-1098.1983","article-title":"Serological evaluation of O fever in humans: Enhanced phase I titers of immunoglobulins G and A are diagnostic for Q fever endocarditis","volume":"41","author":"Peacock","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1128\/cdli.1.2.189-196.1994","article-title":"Q fever serology: Cutoff determination for microimmunofluorescence","volume":"1","author":"Dupont","year":"1994","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1128\/JCM.36.7.1823-1834.1998","article-title":"Diagnosis of Q Fever","volume":"36","author":"Fournier","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_112","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":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.virol.2010.12.016","article-title":"Contributions of humoral and cellular immunity to vaccine-induced protection in humans","volume":"411","author":"Amanna","year":"2011","journal-title":"Virology"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sireci, G., Badami, G.D., Di Liberto, D., Blanda, V., Grippi, F., Di Paola, L., Guercio, A., de la Fuente, J., and Torina, A. (2021). Recent Advances on the Innate Immune Response to Coxiella burnetii. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.754455"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"209.e9","DOI":"10.1016\/j.cmi.2016.11.008","article-title":"Intact interferon-\u03b3 response against Coxiella burnetii by peripheral blood mononuclear cells in chronic Q fever","volume":"23","author":"Schoffelen","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1128\/CMR.12.4.518","article-title":"Q fever","volume":"12","author":"Maurin","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Brooke, R.J., Kretzschmar, M.E., Mutters, N.T., and Teunis, P.F. (2013). Human dose response relation for airborne exposure to Coxiella burnetii. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-488"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1128\/IAI.01208-15","article-title":"Coxiella burnetii Infects Primary Bovine Macrophages and Limits Their Host Cell Response","volume":"84","author":"Sobotta","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1473-3099(05)70052-9","article-title":"Natural history and pathophysiology of Q fever","volume":"5","author":"Raoult","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1097\/00004836-198706000-00024","article-title":"The Pathology of Q Fever Hepatitis: A Case Diagnosed by Liver Biopsy","volume":"9","author":"Westlake","year":"1987","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.medmal.2014.02.006","article-title":"Q fever in the Netherlands\u20142007\u20132010: What we learned from the largest outbreak ever","volume":"44","author":"Schneeberger","year":"2014","journal-title":"Med. Mal. Infect."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.annpat.2012.05.003","article-title":"Fi\u00e8vreQ: Localisationm\u00e9dullaire d\u2019un granulomecaract\u00e9ristique","volume":"32","author":"Szablewski","year":"2012","journal-title":"Ann. Pathol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"43","DOI":"10.11599\/germs.2012.1013","article-title":"cute Q fever in Portugal. Epidemiological and clinical features of 32 hospitalized patients","volume":"2","author":"Palmela","year":"2012","journal-title":"GERMS"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/14787210.2020.1699055","article-title":"New insights in Coxiella burnetii infection: Diagnosis and therapeutic update","volume":"18","author":"Melenotte","year":"2020","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S1473-3099(10)70135-3","article-title":"Long-term outcome of Q fever endocarditis: A 26-year personal survey","volume":"10","author":"Million","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1001\/archinte.1993.00410050074010","article-title":"Chronic Q Fever: Ninety-two Cases from France, Including 27 Cases Without Endocarditis","volume":"153","author":"Brouqui","year":"1993","journal-title":"Arch. Intern. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1469-0691.2008.02213.x","article-title":"Immunohistochemical detection of Coxiella burnetii in an aortic graft","volume":"15","author":"Lepidi","year":"2009","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10096-007-0357-6","article-title":"Coxiella burnetii infection of aortic aneurysms or vascular grafts: Report of 30 new cases and evaluation of outcome","volume":"26","author":"Fournier","year":"2007","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3201\/eid1102.040668","article-title":"Bacterial Zoonoses and Infective Endocarditis, Algeria","volume":"11","author":"Benslimani","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jinf.2014.03.009","article-title":"Estimated prevalence of chronic Q fever among Coxiella burnetii seropositive patients with an abdominal aortic\/iliac aneurysm or aorto-iliac reconstruction after a large Dutch Q fever outbreak","volume":"69","author":"Hagenaars","year":"2014","journal-title":"J. Infect."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1749-6632.2009.04515.x","article-title":"Intracellular Life of Coxiella burnetii in Macrophages: An Update","volume":"1166","author":"Ghigo","year":"2009","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Ka, M.B., Mezouar, S., Ben Amara, A., Raoult, D., Ghigo, E., Olive, D., and Mege, J.-L. (2016). Coxiella burnetii Induces Inflammatory Interferon-Like Signature in Plasmacytoid Dendritic Cells: A New Feature of Immune Response in Q Fever. Front. Cell Infect. Microbiol., 6, Available online: http:\/\/journal.frontiersin.org\/Article\/10.3389\/fcimb.2016.00070\/abstract.","DOI":"10.3389\/fcimb.2016.00070"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5673","DOI":"10.1128\/IAI.68.10.5673-5678.2000","article-title":"\u03b1v \u03b23 Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii -Stimulated Production of Tumor Necrosis Factor by Human Monocytes","volume":"68","author":"Dellacasagrande","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"765","DOI":"10.4269\/ajtmh.12-0212","article-title":"Coxiella burnetii DNA, But Not Viable Bacteria, in Dairy Products in France","volume":"88","author":"Eldin","year":"2013","journal-title":"Am. Soc. Trop. Med. Hyg."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Ben Amara, A., Ghigo, E., Le Priol, Y., L\u00e9polard, C., Salcedo, S.P., Lemichez, E., Bretelle, F., Capo, C., and Mege, J.-L. (2010). Coxiella burnetii, the Agent of Q Fever, Replicates within Trophoblasts and Induces a Unique Transcriptional Response. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015315"},{"key":"ref_136","first-page":"232","article-title":"Ecological study of Ixodes ricinus (Linn\u00e9, 1758) (Acarina, Ixodoides) in southeastern France","volume":"32","author":"Gilot","year":"1975","journal-title":"Acta Trop."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1093\/infdis\/jis013","article-title":"Defective Monocyte Dynamics in Q Fever Granuloma Deficiency","volume":"205","author":"Delaby","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jinf.2014.01.004","article-title":"Serious long-term health consequences of Q-fever and Legionnaires\u2019 disease","volume":"68","author":"Vercoulen","year":"2014","journal-title":"J. Infect."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/15303660260613747","article-title":"Q Fever in Humans and Animals in the United States","volume":"2","author":"McQuiston","year":"2002","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Scholzen, A., Richard, G., Moise, L., Baeten, L.A., Reeves, P.M., Martin, W.D., Brauns, T.A., Boyle, C.M., Paul, S.R., and Bucala, R. (2019). Promiscuous Coxiella burnetii CD4 Epitope Clusters Associated with Human Recall Responses Are Candidates for a Novel T-Cell Targeted Multi-Epitope Q Fever Vaccine. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00207"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1016\/j.vaccine.2007.08.002","article-title":"Coxiella burnetii: Host and bacterial responses to infection","volume":"25","author":"Waag","year":"2007","journal-title":"Vaccine"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Sluder, A.E., Raju Paul, S., Moise, L., Dold, C., Richard, G., Silva-Reyes, L., Baeten, L.A., Scholzen, A., Reeves, P.M., and Pollard, A.J. (2022). Evaluation of a Human T Cell-Targeted Multi-Epitope Vaccine for Q Fever in Animal Models of Coxiella burnetii Immunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.901372"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"611","DOI":"10.4049\/jimmunol.1900991","article-title":"Tuning Subunit Vaccines with Novel TLR Triagonist Adjuvants to Generate Protective Immune Responses against Coxiella burnetii","volume":"204","author":"Gilkes","year":"2020","journal-title":"J. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e00178-19","DOI":"10.1128\/IAI.00178-19","article-title":"Coxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman Primates","volume":"87","author":"Gregory","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/bioe.12773","article-title":"Decision analysis approach to risk\/benefit evaluation in the ethical review of controlled human infection studies","volume":"34","author":"Yu","year":"2020","journal-title":"Bioethics"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1586\/14760584.3.5.577","article-title":"Vaccines against Coxiella infection","volume":"3","author":"Zhang","year":"2004","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_147","first-page":"71","article-title":"Vaccination against Q fever","volume":"47","author":"Smadel","year":"1948","journal-title":"Am. J. Hyg."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/milmed\/129.7.591","article-title":"Recurrent Reaction of Site of Q Fever Vaccination in a Sensitized Person","volume":"129","author":"Bell","year":"1964","journal-title":"Mil. Med."},{"key":"ref_149","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":"Brezina","year":"1982","journal-title":"Bull. World Health Organ."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/j.vaccine.2009.02.007","article-title":"Australia\u2019s national Q fever vaccination program","volume":"27","author":"Gidding","year":"2009","journal-title":"Vaccine"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1128\/JB.00071-13","article-title":"Identification of Coxiella burnetii Type IV Secretion Substrates Required for Intracellular Replication and Coxiella-Containing Vacuole Formation","volume":"195","author":"Weber","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e00175-11","DOI":"10.1128\/mBio.00175-11","article-title":"Dot\/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages","volume":"2","author":"Beare","year":"2011","journal-title":"mBio"},{"key":"ref_153","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":"Chen","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0950268810002268","article-title":"The Q fever epidemic in The Netherlands: History, onset, response and reflection","volume":"139","author":"Roest","year":"2011","journal-title":"Epidemiol. Infect."},{"key":"ref_155","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":"ref_156","doi-asserted-by":"crossref","unstructured":"Fontes, S.D.S., Maia, F.D.M., Ataides, L.S., Conte, F.P., Lima-Junior, J.D.C., Rozental, T., da Silva Assis, M.R., J\u00fanior, A.A.P., Fernandes, J., and de Lemos, E.R.S. (2021). Identification of Immunogenic Linear B-Cell Epitopes in C. burnetii Outer Membrane Proteins Using Immunoinformatics Approaches Reveals Potential Targets of Persistent Infections. Pathogens, 10.","DOI":"10.3390\/pathogens10101250"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1128\/iai.61.4.1251-1258.1993","article-title":"Safety and immunogenicity in human volunteers of a chloroform-methanol residue vaccine for Q fever","volume":"61","author":"Fries","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.1016\/j.vaccine.2019.08.041","article-title":"Enhanced protection against Q fever in BALB\/c mice elicited by immunization of chloroform-methanol residue of Coxiella burnetii via intratracheal inoculation","volume":"37","author":"Feng","year":"2019","journal-title":"Vaccine"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4049\/jimmunol.89.1.145","article-title":"Antigenic and Skin-Reactive Properties of Fractions of Coxiella burnetii","volume":"89","author":"Anacker","year":"1962","journal-title":"J. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"100480","DOI":"10.1016\/j.xcrm.2021.100480","article-title":"Q fever vaccine development: Challenges and progress in balancing safety and efficacy","volume":"2","author":"Sluder","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"107136","DOI":"10.1016\/j.micpath.2024.107136","article-title":"Computational studies on metabolic pathways of Coxiella burnetii to combat Q fever: A roadmap to vaccine development","volume":"198","author":"Sharma","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Fratzke, A.P., van Schaik, E.J., and Samuel, J.E. (2022). Immunogenicity and Reactogenicity in Q Fever Vaccine Development. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.886810"},{"key":"ref_163","first-page":"341","article-title":"Cloning and Expression of Com1 and OmpH Genes of Coxiella burnetii in Periplasmic Compartment of Escherichia coli with Purpose of Recombinant Subunit Vaccine Production","volume":"74","author":"Bakhteyari","year":"2019","journal-title":"Arch. Razi Inst."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Van Hoeven, N., Joshi, S.W., Nana, G.I., Bosco-Lauth, A., Fox, C., Bowen, R.A., Clements, D.E., Martyak, T., Parks, D.E., and Baldwin, S. (2016). A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149610"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1128\/iai.32.2.840-851.1981","article-title":"Immunological and biological characterization of Coxiella burnetii, phases I and II, separated from host components","volume":"32","author":"Williams","year":"1981","journal-title":"Infect. Immun."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.4049\/jimmunol.1201622","article-title":"Development of a Lipopolysaccharide-Targeted Peptide Mimic Vaccine against Q Fever","volume":"189","author":"Peng","year":"2012","journal-title":"J. Immunol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.4161\/hv.26088","article-title":"Advances in the study of HLA-restricted epitope vaccines","volume":"9","author":"Zhao","year":"2013","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e2302351","DOI":"10.1002\/adhm.202302351","article-title":"Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever","volume":"13","author":"Sam","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Amin, A., Farid, A., Ullah, A., Waris, A., Shinwari, K., Hussain, Y., Alsharif, K.F., Alzahrani, K.J., and Khan, H. (2022). Recent Advances in Genomics-Based Approaches for the Development of Intracellular Bacterial Pathogen Vaccines. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010152"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Filipi\u0107, B., Panteli\u0107, I., Nikoli\u0107, I., Majhen, D., Stoji\u0107-Vukani\u0107, Z., Savi\u0107, S., and Kraji\u0161nik, D. (2023). Nanoparticle-Based Adjuvants and Delivery Systems for Modern Vaccines. Vaccines, 11.","DOI":"10.3390\/vaccines11071172"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Kozak, M., and Hu, J. (2024). DNA Vaccines: Their Formulations, Engineering and Delivery. Vaccines, 12.","DOI":"10.3390\/vaccines12010071"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1146\/annurev.immunol.18.1.927","article-title":"DNA Vaccines: Immunology, Application, and Optimization","volume":"18","author":"Gurunathan","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1146\/annurev.immunol.15.1.617","article-title":"DNA Vaccines","volume":"15","author":"Donnelly","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1515\/BC.2001.068","article-title":"Revealing the Potential of DNA-Based Vaccination: Lessons Learned from the Hepatitis B Virus Surface Antigen","volume":"382","author":"Schirmbeck","year":"2001","journal-title":"Biol. Chem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1586\/14760584.2016.1124762","article-title":"Molecular mechanisms for enhanced DNA vaccine immunogenicity","volume":"15","author":"Li","year":"2016","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/82_2021_233","article-title":"Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action","volume":"Volume 440","author":"Yu","year":"2021","journal-title":"mRNA Vaccines"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Brito, L.A., Kommareddy, S., Maione, D., Uematsu, Y., Giovani, C., BerlandaScorza, F., Otten, G.R., Yu, D., Mandl, C.W., and Mason, P.W. (2015). Self-Amplifying mRNA Vaccines. Advances in Genetics, Elsevier.","DOI":"10.1016\/bs.adgen.2014.10.005"},{"key":"ref_178","first-page":"491","article-title":"mRNA vaccines: Past, present, future","volume":"17","author":"Karam","year":"2022","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2001812","DOI":"10.1002\/adhm.202001812","article-title":"Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery","volume":"10","author":"Ho","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.omtm.2022.03.009","article-title":"A flexible, thermostable nanostructured lipid carrier platform for RNA vaccine delivery","volume":"25","author":"Gerhardt","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.humimm.2020.05.010","article-title":"Computational design of a novel multi-epitope vaccine against Coxiella burnetii","volume":"81","author":"Jaydari","year":"2020","journal-title":"Hum. Immunol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.2174\/1381612829666230418104520","article-title":"Immunoinformatics and Reverse Vaccinology Driven Predication of a Multi-epitope Vaccine against Borrelia burgdorferi and Validation through in silico Cloning and Immune Simulation","volume":"29","author":"Hussain","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10989-008-9147-y","article-title":"Recent Advances in Design and Synthesis of Self-Adjuvanting Lipopeptide Vaccines","volume":"14","author":"Toth","year":"2008","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/1097-0282(2000)55:3<227::AID-BIP50>3.0.CO;2-7","article-title":"Large-scale synthesis of peptides","volume":"55","author":"Andersson","year":"2000","journal-title":"Biopolymers"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"168","DOI":"10.31857\/S0026898422010037","article-title":"\u041ao\u043d\u0441\u0442\u0440\u0443\u0438\u0440o\u0432\u0430\u043d\u0438\u0435 in silico \u043do\u0432o\u0439 \u043c\u0443\u043b\u044c\u0442\u0438\u044d\u043f\u0438\u0442o\u043f\u043do\u0439 \u043a\u0430\u043d\u0434\u0438\u0434\u0430\u0442\u043do\u0439 \u043f\u0435\u043f\u0442\u0438\u0434\u043do\u0439 \u0432\u0430\u043a\u0446\u0438\u043d\u044b \u043f\u0440o\u0442\u0438\u0432 Q-\u043b\u0438\u0445o\u0440\u0430\u0434\u043a\u0438","volume":"56","author":"Jabarzadeh","year":"2022","journal-title":"\u041co\u043b\u0435\u043a\u0443\u043b\u044f\u0440\u043d\u0430\u044f \u0431\u0438o\u043bo\u0433\u0438\u044f"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1007\/s11095-014-1419-y","article-title":"Biomaterials for Nanoparticle Vaccine Delivery Systems","volume":"31","author":"Sahdev","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"181.03","DOI":"10.4049\/jimmunol.208.Supp.181.03","article-title":"Assessing Immunogenicity of Vaccines and Adjuvant Combinations for Q Fever","volume":"208","author":"Jan","year":"2022","journal-title":"J. Immunol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd1176","article-title":"Recent advances in the discovery and delivery of vaccine adjuvants","volume":"2","author":"Valiante","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1016\/j.vaccine.2017.02.069","article-title":"Platform technologies for modern vaccine manufacturing","volume":"35","author":"Lua","year":"2017","journal-title":"Vaccine"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1080\/21645515.2021.1911204","article-title":"COVID-19 vaccine platforms: Delivering on a promise?","volume":"17","author":"Verdecia","year":"2021","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"704","DOI":"10.5694\/j.1326-5377.1994.tb125909.x","article-title":"Vaccine prophylaxis of Q fever. A follow-up study of the efficacy of Q-Vax (CSL) 1985-1990","volume":"160","author":"Ackland","year":"1994","journal-title":"Med. J. Aust."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/j.1467-842X.2003.tb00415.x","article-title":"An economic evaluation of increased uptake in Q fever vaccination among meat and agricultural industry workers following implementation of the National Q Fever Management Program","volume":"27","author":"Kermode","year":"2003","journal-title":"Aust. N. Z. J. Public Health"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S0950268811000136","article-title":"Low seroprevalence of Q fever in The Netherlands prior to a series of large outbreaks","volume":"140","author":"Schimmer","year":"2012","journal-title":"Epidemiol. Infect."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/2\/151\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:04Z","timestamp":1760027104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/2\/151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":193,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["vaccines13020151"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13020151","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}