{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:14:20Z","timestamp":1791087260532,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Although the phase I<jats:italic>Coxiella burnetii<\/jats:italic>cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to<jats:italic>C. burnetii<\/jats:italic>received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 \u03bcg, followed by a booster dose of 30 \u03bcg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-<jats:italic>C. burnetii<\/jats:italic>antibody. Peripheral blood cells (PBCs) of vaccinees responded to<jats:italic>C. burnetii<\/jats:italic>cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection.<\/jats:p>","DOI":"10.1128\/cvi.00119-08","type":"journal-article","created":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T01:30:02Z","timestamp":1218677402000},"page":"1505-1512","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Low-Dose Priming before Vaccination with the Phase I Chloroform-Methanol Residue Vaccine against Q Fever Enhances Humoral and Cellular Immune Responses to<i>Coxiella burnetii<\/i>"],"prefix":"10.1128","volume":"15","author":[{"given":"David M.","family":"Waag","sequence":"first","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn J.","family":"England","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Bolt","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim C.","family":"Williams","sequence":"additional","affiliation":[{"name":"Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.5694\/j.1326-5377.1994.tb125909.x","volume":"160","year":"1994","unstructured":"Ackland, J. R., D. A. Worswick, and B. P. Marmion. 1994. Vaccine prophylaxis of Q fever. A follow-up study of the efficacy of Q-Vax (CSL) 1985-1990. Med. J. Aust.160:704-708.","journal-title":"Med. J. Aust."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.160.3.994-1002.1984"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/milmed\/129.7.591","volume":"129","year":"1964","unstructured":"Bell, J. F., D. B. Lackman, A. Meis, and W. J. Hadlow. 1964. Recurrent reaction of site of Q fever vaccination in a sensitized person. Mil. Med.129:591-595.","journal-title":"Mil. Med."},{"key":"e_1_3_2_5_2","first-page":"47","year":"1959","unstructured":"Benenson, A. S. 1959. Q fever vaccine: efficacy and present status, p. 47-60. In J. E. Smadel (ed.), Symposium on Q fever. Walter Reed Army Institute of Medical Science publication no. 6. Government Printing Office, Washington, DC.","journal-title":"Symposium on Q fever."},{"key":"e_1_3_2_6_2","first-page":"269","volume":"18","year":"1974","unstructured":"Brezina, R., S. Schramek, J. Kazar, and J. Urovolgyi. 1974. Q fever chemovaccine for human use. Acta Virol.18:269.","journal-title":"Acta Virol."},{"key":"e_1_3_2_7_2","first-page":"1235","volume":"47","year":"1986","unstructured":"Brooks, D. L., R. W. Ermel, C. E. Franti, R. Ruppanner, D. E. Behymer, J. C. Williams, E. H. Stephenson, and J. C. Stephenson. 1986. Q fever vaccination of sheep: challenge of immunity in ewes. Am. J. Vet. Res.47:1235-1238.","journal-title":"Am. J. Vet. Res."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.5694\/j.1326-5377.1937.tb43744.x","volume":"2","year":"1937","unstructured":"Burnet, F. M., and M. Freeman. 1937. Experimental studies on the virus of \u201cQ\u201d fever. Med. J. Aust.2:299-305.","journal-title":"Med. J. Aust."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.5694\/j.1326-5377.1937.tb43743.x","volume":"2","year":"1937","unstructured":"Derrick, E. H. 1937. Q fever, a new fever entity: clinical features, diagnosis and laboratory investigation. Med. J. Aust.2:281-299.","journal-title":"Med. J. Aust."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.22.4.484-487.1985"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1139\/m90-050","volume":"36","year":"1990","unstructured":"Embil, J., J. C. Williams, and T. J. Marrie. 1990. The immune response in a cat-related outbreak of Q fever as measured by the indirect immunofluorescence test and the enzyme-linked immunosorbent assay. Can. J. Microbiol.36:292-296.","journal-title":"Can. J. Microbiol."},{"key":"e_1_3_2_12_2","first-page":"528","year":"1966","unstructured":"Fiset, P. 1966. Vaccination against Q fever, p. 528-531. In Vaccines against viral and rickettsial diseases in man. PAHO science publication number 147. Pan American Health Organization, Washington, DC.","journal-title":"PAHO science publication number 147."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.4.1251-1258.1993"},{"key":"e_1_3_2_14_2","first-page":"703","volume":"10","year":"1965","unstructured":"Genig, V. A. 1965. Experience in mass immunization of humans with the M-44 live vaccine against Q-fever. 2. Skin and oral routes of immunization. Vopr. Virusol.10:703-707.","journal-title":"Vopr. Virusol."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/infdis\/133.3.334","volume":"133","year":"1976","unstructured":"Johnson, J. W., G. A. Eddy, and C. E. Pedersen, Jr. 1976. Biological properties of the M-44 strain of Coxiella burnetii. J. Infect. Dis.133:334-338.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_16_2","first-page":"48","volume":"31","year":"1981","unstructured":"Kishimoto, R. A., J. C. Gonder, J. W. Johnson, J. A. Reynolds, and E. W. Larson. 1981. Evaluation of a killed phase I Coxiella burnetii vaccine in cynomolgus monkeys (Macaca fascicularis). Lab. Anim. Sci.31:48-51.","journal-title":"Lab. Anim. Sci."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.4049\/jimmunol.135.2.1067","volume":"135","year":"1985","unstructured":"Koster, F. T., J. C. Williams, and J. S. Goodwin. 1985. Cellular immunity in Q fever: modulation of responsiveness by a suppressor T cell-monocyte circuit. J. Immunol.135:1067-1072.","journal-title":"J. Immunol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2105\/AJPH.52.1.87","volume":"52","year":"1962","unstructured":"Lackman, D., E. J. Bell, J. F. Bell, and E. Pickens. 1962. Intradermal sensitivity testing in man with a purified vaccine for Q fever. Am. J. Public Health52:87-93.","journal-title":"Am. J. Public Health"},{"key":"e_1_3_2_19_2","first-page":"1","volume":"78","year":"1963","unstructured":"Luoto, L., J. F. Bell, M. L. Casey, and D. B. Lackman. 1963. Q fever vaccination of human volunteers. I. The serologic and skin test response following subcutaneous injections. Am. J. Hyg.78:1-15.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_20_2","first-page":"225","year":"1990","unstructured":"Ormsbee, R., and B. Marmion. 1990. Prevention of Coxiella burnetii infection: vaccines and guidelines for those at risk, p. 225-248. In T. Marrie (ed.), Q fever. The disease, vol. I. CRC Press, Boca Raton, FL.","journal-title":"Q fever."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.4049\/jimmunol.88.6.741","volume":"88","year":"1962","unstructured":"Ormsbee, R. A., E. J. Bell, and D. B. Lackman. 1962. Antigens of Coxiella burnetii. I. Extraction of antigens with non-aqueous organic solvents. J. Immunol.88:741-749.","journal-title":"J. Immunol."},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4049\/jimmunol.92.3.404","volume":"92","year":"1964","unstructured":"Ormsbee, R. A., E. J. Bell, D. B. Lackman, and G. Tallent. 1964. The influence of phase on the protective potency of Q fever vaccine. J. Immunol.92:404-412.","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","first-page":"19","year":"1965","unstructured":"Pollok, N. L. 1965. Mixed infections of staphylococcal enterotoxin B, VEE, and Q fever in Macaca mullata monkeys, p. 19. Technical manuscript no. 237. U.S. Army Laboratories, Fort Detrick, MD.","journal-title":"Technical manuscript no. 237."},{"key":"e_1_3_2_24_2","first-page":"26","year":"1962","unstructured":"Pollok, N. L. 1962. Mixed infections of Venezuelan equine encephalomyelitis and Q fever in Macaca mullata monkeys, p. 26. Technical memorandum no. 28. U.S. Army Biological Laboratories, Ft. Detrick, MD.","journal-title":"Technical memorandum no. 28."},{"key":"e_1_3_2_25_2","first-page":"3263","volume":"135","year":"1989","unstructured":"Scott, G. H., T. F. McCaul, and J. C. Williams. 1989. Inactivation of Coxiella burnetii by gamma irradiation. J. Gen. Microbiol.135:3263-3270.","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_2_26_2","first-page":"71","volume":"47","year":"1948","unstructured":"Smadel, J. E., M. J. Snyder, and F. C. Robins. 1948. Vaccination against Q fever. Am. J. Hyg.47:71-78.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.32.1.85-88.1976"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1136\/bmj.1.5016.425","volume":"1","year":"1957","unstructured":"Stoker, M. G. P. 1957. Q fever down the drain. Br. Med. J.1:425-427.","journal-title":"Br. Med. J."},{"key":"e_1_3_2_29_2","first-page":"39","volume":"6","year":"1959","unstructured":"Tigertt, W. D. 1959. Studies on Q fever in man, p. 39. In J. E. Smadel (ed.), Symposium on Q fever,vol. 6. U.S. Government Printing Office, Washington, DC.","journal-title":"Symposium on Q fever"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0003-2697(82)90673-X","volume":"119","year":"1982","unstructured":"Tsai, C. M., and C. E. Frasch. 1982. A sensitive silver stain for detecting lipopolysaccharides in polyacrylamide gels. Anal. Biochem.119:115-119.","journal-title":"Anal. Biochem."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.6.1560-1565.1994"},{"key":"e_1_3_2_32_2","first-page":"143","volume":"79","year":"1964","unstructured":"Vivona, S., J. P. Lowenthal, S. Berman, A. S. Benenson, and J. E. Smadel. 1964. Report of a field study with Q fever vaccine. Am. J. Hyg.79:143-153.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/BF02114898","volume":"14","year":"1995","unstructured":"Waag, D., J. Chulay, T. Marrie, M. England, and J. Williams. 1995. Validation of an enzyme immunoassay for serodiagnosis of acute Q fever. Eur. J. Clin. Microbiol. Infect. Dis.14:421-427.","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"e_1_3_2_34_2","first-page":"157","year":"1991","unstructured":"Waag, D. M., C. R. Bolt, T. J. Marrie, and J. C. Williams. 1991. Specific responses of humans to Coxiella burnetii: specific antibody and cell-mediated responses after vaccination or infection, p. 157-173. In J. C. Williams and H. A. Thompson (ed.), Q fever: the biology of Coxiella burnetii. CRC Press, Boca Raton, FL.","journal-title":"Q fever: the biology of Coxiella burnetii."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1016\/S0264-410X(97)00107-2","volume":"15","year":"1997","unstructured":"Waag, D. M., M. J. England, and M. L. Pitt. 1997. Comparative efficacy of a Coxiella burnetii chloroform:methanol residue (CMR) vaccine and a licensed cellular vaccine (Q-Vax) in rodents challenged by aerosol. Vaccine15:1779-1783.","journal-title":"Vaccine"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.2.2.143-148.1995"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.22.2.627-628.1978"},{"key":"e_1_3_2_38_2","first-page":"374","volume":"50","year":"2000","unstructured":"Wilhelmsen, C. L., and D. M. Waag. 2000. Guinea pig abscess\/hypersensitivity model for study of adverse vaccination reactions induced by use of Q fever vaccines. Comp. Med.50:374-378.","journal-title":"Comp. Med."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.35.3.1091-1102.1982"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.51.3.851-858.1986"},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/j.1749-6632.1990.tb42243.x","volume":"590","year":"1990","unstructured":"Williams, J. C., T. A. Hoover, D. M. Waag, N. Banerjee-Bhatnagar, C. R. Bolt, and G. H. Scott. 1990. Antigenic structure of Coxiella burnetii. A comparison of lipopolysaccharide and protein antigens as vaccines against Q fever. Ann. N. Y. Acad. Sci.590:370-380.","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.32.2.840-851.1981"},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1749-6632.1992.tb19633.x","volume":"653","year":"1992","unstructured":"Williams, J. C., M. G. Peacock, D. M. Waag, G. Kent, M. J. England, G. Nelson, and E. H. Stephenson. 1992. Vaccines against coxiellosis and Q fever. Development of a chloroform:methanol residue subunit of phase I Coxiella burnetii for the immunization of animals. Ann. N. Y. Acad. Sci.653:88-111.","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.24.6.929-934.1986"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00119-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00119-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T16:06:06Z","timestamp":1684512366000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00119-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["10.1128\/CVI.00119-08"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00119-08","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10]]},"assertion":[{"value":"2008-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}