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全细胞百日咳疫苗初次免疫后用于青少年加强免疫时无细胞百日咳疫苗免疫反应的实验室研究:与临床研究数据的比较

Laboratory investigation of immune responses to acellular pertussis vaccines when used for boosting adolescents after primary immunisation with whole cell pertussis vaccines: a comparison with data from clinical study.

作者信息

Reynolds Elinor, Walker Barry, Xing Dorothy, Southern Joanna, Asokanathan Catpagavalli, Dagg Belinda, Corbel Michael, Miller Elizabeth

机构信息

National Institute for Biological Standards and Control, Division of Bacteriology, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.

出版信息

Vaccine. 2006 Apr 12;24(16):3248-57. doi: 10.1016/j.vaccine.2006.01.021. Epub 2006 Jan 25.

Abstract

The lack of unequivocal immunological correlates of human protection and an absence of a validated animal model for acellular pertussis vaccines, compounded by limited opportunity to undertake efficacy studies in humans and laboratory evaluation side by side, has made it difficult to compare vaccines and formulations. In the present study, the effect on the booster response to pertussis in adolescents primed in infancy with whole cell pertussis vaccine, of three low dose acellular pertussis/diphtheria/tetanus toxoid (TdPa) formulations with or without inactivated poliomyelitis vaccine (IPV) components, was investigated. To assess the relationship between laboratory vaccine evaluation and clinical trial performance, parallel evaluation of the same TdPa vaccines were carried out in a mouse booster model with whole cell pertussis vaccine priming. Prior to boosting, the clinical subjects had low cell mediated immune responses (CMI) responses to pertussis vaccine components. After boosting, all TdPa formulations stimulated CMI responses to the pertussis vaccine components assessed. The booster responses to the pertussis antigens remained skewed towards Th1 type even though acellular pertussis vaccines were used. In general the antibody and CMI responses to pertussis antigens in the mouse model followed the trend seen in the human subjects. Protection against aerosol challenge with virulent Bordetella pertussis was related to the magnitude of the antibody and CMI responses in the mouse model. As in the human subjects, the responses remained skewed towards Th1 type.

摘要

缺乏明确的人体保护免疫学关联指标,且无经过验证的无细胞百日咳疫苗动物模型,同时在人体进行疗效研究和实验室评估的机会有限,这些因素共同导致难以比较疫苗及其配方。在本研究中,调查了三种含或不含灭活脊髓灰质炎疫苗(IPV)成分的低剂量无细胞百日咳/白喉/破伤风类毒素(TdPa)配方,对婴儿期接种全细胞百日咳疫苗的青少年百日咳加强免疫反应的影响。为评估实验室疫苗评估与临床试验表现之间的关系,在以全细胞百日咳疫苗进行初免的小鼠加强免疫模型中,对相同的TdPa疫苗进行了平行评估。在加强免疫前,临床受试者对百日咳疫苗成分的细胞介导免疫反应(CMI)较低。加强免疫后,所有TdPa配方均刺激了对所评估的百日咳疫苗成分的CMI反应。尽管使用的是无细胞百日咳疫苗,但对百日咳抗原的加强免疫反应仍偏向Th1型。总体而言,小鼠模型中对百日咳抗原的抗体和CMI反应趋势与人体受试者一致。小鼠模型中针对强毒百日咳博德特氏菌气溶胶攻击的保护作用与抗体和CMI反应的强度相关。与人体受试者一样,反应仍偏向Th1型。

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