Cassone A, Ausiello C M, Urbani F, Lande R, Giuliano M, La Sala A, Piscitelli A, Salmaso S
Department of Bacteriology and Medical Mycology, Rome, Italy, Instituto Superiore di Sanitá, Rome, Italy.
Arch Pediatr Adolesc Med. 1997 Mar;151(3):283-9. doi: 10.1001/archpedi.1997.02170400069013.
To examine induction and persistence of cell-mediated immunity (CMI) and antibody responses to Bordetella pertussis antigens in infants receiving antipertussis vaccines.
A randomized, blinded study of 142 children receiving acellular pertussis vaccines combined with diphtheria-tetanus toxoids (DTaP) (DTaP manufactured by SmithKline Beecham [DTaP-SB], Rixensart, Belgium, and DTaP manufactured by Chiron Biocin [DTaP-CB], Siena, Italy), or a whole-cell pertussis vaccine (DTwP) (Connaught Laboratories Inc, Swiftwater, Pa), or a diphtheria-tetanus (DT) (Chiron Biocine) only vaccine. Three doses of each vaccine were given at 2, 4, and 6 months of age, and CMI and antibody responses were evaluated before and at 1 and 14 months after vaccination.
Cell-mediated immunity was assessed by proliferation of peripheral blood mononuclear cells stimulated in vitro by B pertussis antigens (pertussis toxin, filamentous hemagglutinin, and pertactin). Antibody titers against pertussis toxin, filamentous hemagglutinin, and pertactin were determined by a standardized enzyme-linked immunosorbent assay.
A CMI-positive response to at least 1 B pertussis antigen at 1 or both postvaccination assays was detected in 46%, 55%, and 83% of DTwP, DTaP-SB, and DTaP-CB vaccine recipients, respectively. Frequency of CMI response to individual antigens ranged from less than 4.9% against pertussis toxin in DTwP recipients to 52% against pertactin in DTaP-CB recipients. The postvaccination responses measured at 14 months equalled, or had increased frequency or intensity, that of the 1-month postvaccination responses. Elevated antibody titers against the 3 antigens were present in all DTaP recipients 1 month after vaccination and were higher in CMI-positive children than in CMI-negative children. They fell, however, to low, if not negligible, levels 14 months after vaccination.
Acellular pertussis vaccines were better inducers of CMI response than the whole-cell vaccine, particularly against pertussis toxin. Once acquired, CMI persisted, in contrast with the rapid antibody decline. Thus, CMI responses could be a useful adjunct to serology in the evaluation of pertussis vaccine immunogenicity and a better correlate of long-term immunity to B pertussis than antibody titers.
检测接种抗百日咳疫苗的婴儿中细胞介导免疫(CMI)的诱导及持续情况以及对百日咳博德特氏菌抗原的抗体反应。
一项针对142名儿童的随机、盲法研究,这些儿童分别接种了无细胞百日咳疫苗与白喉破伤风类毒素联合疫苗(DTaP)(由比利时里克森萨特的史克必成公司生产的DTaP [DTaP-SB]、意大利锡耶纳的凯龙生物公司生产的DTaP [DTaP-CB]),或全细胞百日咳疫苗(DTwP)(宾夕法尼亚州斯威夫特沃特的康诺特实验室公司生产),或仅接种白喉破伤风(DT)(凯龙生物公司生产)疫苗。每种疫苗在2、4和6月龄时各接种3剂,并在接种前、接种后1个月和14个月评估CMI和抗体反应。
通过体外百日咳博德特氏菌抗原(百日咳毒素、丝状血凝素和百日咳黏附素)刺激外周血单个核细胞的增殖来评估细胞介导免疫。采用标准化酶联免疫吸附测定法测定针对百日咳毒素、丝状血凝素和百日咳黏附素的抗体滴度。
在接种DTwP、DTaP-SB和DTaP-CB疫苗的儿童中,分别有46%、55%和83%在接种后1次或2次检测中对至少1种百日咳博德特氏菌抗原出现CMI阳性反应。对各抗原的CMI反应频率范围从接种DTwP的儿童中针对百日咳毒素的反应频率低于4.9%到接种DTaP-CB的儿童中针对百日咳黏附素的反应频率为52%。在14个月时测量的接种后反应与接种后1个月的反应相当,或反应频率或强度有所增加。所有接种DTaP的儿童在接种后1个月均出现针对这3种抗原的抗体滴度升高,且CMI阳性儿童的抗体滴度高于CMI阴性儿童。然而,接种后14个月,抗体滴度降至低水平(即使不是可忽略不计的水平)。
无细胞百日咳疫苗比全细胞疫苗更能诱导CMI反应,尤其是针对百日咳毒素。一旦获得,CMI会持续存在,这与抗体迅速下降形成对比。因此,CMI反应在评估百日咳疫苗免疫原性方面可能是血清学的有用辅助手段,并且比抗体滴度更能反映对百日咳博德特氏菌的长期免疫力。