title: Safety and immunogenicity in human volunteers of a chloroform-methanol residue vaccine for Q fever.
abstract: Current Q fever vaccines, consisting of Formalin-inactivated phase I whole Coxiella burnetii, are highly efficacious in preventing disease in high-risk settings but are associated with a risk of unacceptable local reactions in previously immune individuals and require cumbersome preliminary immunologic evaluation of potential vaccinees. A vaccine prepared from the residue of chloroform-methanol extraction of phase I Henzerling strain C. burnetii (CMR) has been shown to be less reactogenic but still immunogenic and protective in small animals and sheep. In a placebo-controlled trial, we immunized 35 healthy adults unscreened for markers of prior C. burnetii immunity with a single subcutaneous CMR dose of 30, 60, 120, or 240 micrograms. None of those receiving the 30- or 60-micrograms CMR dose and none of the placebo recipients experienced any adverse effects. Five of 15 120-micrograms dose CMR recipients complained of transient discomfort in the inoculated arm; erythema or induration of > or = 100 mm2 was noted in three and four, respectively, and two had malaise and low-grade fever (< 101 degrees F, orally). No 240-micrograms dose vaccinee reported limb discomfort, but 7 of 10 had erythema and/or induration of > or = 100 mm2 (P < 0.001 versus placebo). Two reported malaise, and one had low-grade fever. All adverse effects were self-limited. Serum immunoglobulin M responses were optimally detected with CMR antigen and occurred in 50, 60, 73, and 90% of recipients of the 30-, 60-, 120-, and 240-micrograms doses, respectively; results with phase I whole-cell antigen were similar. Serum immunoglobulin G responses were best detected with phase II antigen and were seen in 20, 20, and 40% of those receiving the 60-, 120-, and 240-micrograms doses, respectively. Peripheral blood T-cell proliferative responses to C. burnetii recall antigens were transient and of low magnitude but were seen with CMR antigen in 33% of 120-micrograms dose recipients and 40% of 240-micrograms dose recipients. Data from this study and those from comparative-efficacy trials in primates should provide the basis for field trials of the CMR vaccine.
authors.affiliation: Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
authors.forename: L F
authors.initials: LF
authors.lastname: Fries
authors.forename: D M
authors.initials: DM
authors.lastname: Waag
authors.forename: J C
authors.initials: JC
authors.lastname: Williams
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000737:chemistry / Q000592:standards*; D002725:Chloroform; D016997:Coxiella burnetii / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D000432:Methanol; D011778:Q Fever / Q000517:prevention & control*; D013997:Time Factors; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D002725:Chloroform; D000432:Methanol