Greco D, Salmaso S, Mastrantonio P, Giuliano M, Tozzi A E, Anemona A, Ciofi degli Atti M L, Giammanco A, Panei P, Blackwelder W C, Klein D L, Wassilak S G
Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Rome, Italy.
N Engl J Med. 1996 Feb 8;334(6):341-8. doi: 10.1056/NEJM199602083340601.
Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low.
We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing.
The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group.
The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.
对安全性和有效性的担忧使得全细胞百日咳疫苗的使用存在争议。在包括意大利在内的一些欧洲国家，百日咳疫苗接种率较低。
我们在意大利进行了一项双盲试验，将婴儿在2、4和6月龄时随机分配，分别接种含无细胞百日咳疫苗以及白喉和破伤风类毒素的疫苗（DTP）；含全细胞百日咳的DTP疫苗（由康诺特实验室生产）；或不含百日咳的白喉和破伤风类毒素（DT）。无细胞DTP疫苗一种含有丝状血凝素、百日咳杆菌黏附素以及经福尔马林和戊二醛灭活的百日咳毒素（史克必成公司），另一种含有丝状血凝素、百日咳杆菌黏附素以及经基因解毒的百日咳毒素（奇隆生物制药公司）。百日咳定义为阵发性咳嗽持续21天或更长时间，通过培养或血清学检测确认感染。
对14751名儿童平均随访17个月，确定了每种疫苗3剂接种后预防百日咳的效力，若咳嗽在免疫完成30天或更长时间后开始，则病例纳入分析。两种无细胞DTP疫苗的效力均为84%（95%置信区间，生物制药公司DTP为76%至89%，史克必成公司DTP为76%至90%），而全细胞DTP疫苗的效力仅为36%（95%置信区间，14%至52%）。无细胞疫苗的抗体反应大于全细胞疫苗。全细胞疫苗接种后局部和全身不良事件明显更频繁。对于无细胞疫苗，不良事件发生率与对照组（DT）相似。
我们研究的两种无细胞DTP疫苗安全、具有免疫原性且对百日咳有效，而全细胞DTP疫苗的效力出人意料地低。
