Fries L F, Waag D M, Williams J C
Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Infect Immun. 1993 Apr;61(4):1251-8. doi: 10.1128/iai.61.4.1251-1258.1993.
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.
目前的Q热疫苗由福尔马林灭活的I期全贝氏柯克斯体组成，在预防高危环境中的疾病方面非常有效，但与既往免疫个体出现不可接受的局部反应风险相关，并且需要对潜在接种者进行繁琐的初步免疫学评估。一种由I期亨泽林菌株贝氏柯克斯体氯仿 - 甲醇提取物（CMR）制备的疫苗已被证明在小动物和绵羊中反应原性较低，但仍具有免疫原性和保护性。在一项安慰剂对照试验中，我们对35名未筛查既往贝氏柯克斯体免疫标志物的健康成年人皮下注射单剂量30、60、120或240微克的CMR。接受30微克或60微克CMR剂量的人以及安慰剂接受者均未出现任何不良反应。15名接受120微克剂量CMR的人中，有5人抱怨接种手臂出现短暂不适；分别有3人和4人出现红斑或硬结面积≥100平方毫米，2人出现不适和低热（口服体温<101华氏度）。接受240微克剂量疫苗的人中无人报告肢体不适，但10人中有7人出现红斑和/或硬结面积≥100平方毫米（与安慰剂相比，P<0.001）。2人报告不适，1人出现低热。所有不良反应均为自限性。用CMR抗原能最佳检测到血清免疫球蛋白M反应，分别在接受30微克、60微克、120微克和240微克剂量的接种者中发生率为50%、60%、73%和90%；I期全细胞抗原检测结果相似。用II期抗原能最佳检测到血清免疫球蛋白G反应，分别在接受60微克、120微克和240微克剂量的人中发生率为20%、20%和40%。外周血T细胞对贝氏柯克斯体回忆抗原的增殖反应短暂且程度低，但在接受120微克剂量的接种者中有33%以及接受240微克剂量的接种者中有40%在用CMR抗原检测时出现反应。本研究的数据以及灵长类动物比较疗效试验的数据应为CMR疫苗的现场试验提供依据。
