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无细胞百日咳疫苗以及百日咳杆菌粘附素和菌毛的作用。

Acellular pertussis vaccines and the role of pertactin and fimbriae.

作者信息

Poolman Jan T, Hallander Hans O

机构信息

Head of Bacterial Vaccines, R&D Bacterial Vaccine Program, GlaxoSmithKline Biologicals, Rixensart, Belgium.

出版信息

Expert Rev Vaccines. 2007 Feb;6(1):47-56. doi: 10.1586/14760584.6.1.47.

Abstract

The introduction of acellular pertussis (Pa) vaccines in countries with a low uptake of whole-cell pertussis (Pw) vaccines has led to a dramatic reduction in pertussis disease. Diphtheria-tetanus-acellular pertussis (DTPa) vaccines have also ensured continued high level disease protection in these countries following the shift from Pw- to Pa-containing vaccines, and allowed pertussis booster programs to be implemented. Vaccines containing between one and five components have been licensed and implemented. Those with three or more components consisting of filamentous hemagglutinin (FHA), pertussis toxin (PT) and pertactin (PRN) are considered to be more effective than one/two-component Pa vaccines that contain only PT or both PT and FHA. Changes in circulating Bordetella pertussis strains may impact vaccine efficacy and, thus, incidence and transmission of pertussis and deserve to be followed carefully. To date, vaccine-induced shifts among fimbriae (FIM) are reported and this could impact the efficacy of FIM-containing vaccines. Currently, FIM3 appears to be dominant in most European countries, Canada and Australia. Data obtained from a DTPa5 vaccine containing FIM2 and FIM3 have indicated a shift towards an increase in FIM3-expressing B. pertussis clinical breakthrough cases when compared with control vaccine. By contrast, relatively minor PT and PRN sequence polymorphisms have been identified without demonstrable association with vaccination programs. Adsorption of PRN to aluminum salt appears critical for optimal protective capacity in murine pertussis lung challenge. In addition, clinical studies have shown anti-PRN antibody levels to be higher when PRN is adsorbed at a 8-microg dosage versus non-adsorbed PRN at a 3-microg dosage. The available data, therefore, demonstrate that appropriately formulated acellular vaccines containing PT and PRN are the preferred option for pertussis immunization.

摘要

在全细胞百日咳(Pw)疫苗接种率较低的国家引入无细胞百日咳(Pa)疫苗后,百日咳疾病显著减少。白喉-破伤风-无细胞百日咳(DTPa)疫苗在这些国家从含Pw疫苗向含Pa疫苗转变后,也确保了持续的高水平疾病防护,并使百日咳加强免疫计划得以实施。含有一至五种成分的疫苗已获许可并投入使用。含有丝状血凝素(FHA)、百日咳毒素(PT)和百日咳杆菌黏附素(PRN)三种或更多成分的疫苗被认为比仅含PT或同时含PT和FHA的一/二组分Pa疫苗更有效。循环中的百日咳博德特氏菌菌株的变化可能影响疫苗效力,进而影响百日咳的发病率和传播,值得密切关注。迄今为止,已有关于疫苗诱导的菌毛(FIM)变化的报道,这可能影响含FIM疫苗的效力。目前,FIM3在大多数欧洲国家、加拿大和澳大利亚似乎占主导地位。从含FIM2和FIM3的DTPa5疫苗获得的数据表明,与对照疫苗相比,表达FIM3的百日咳博德特氏菌临床突破病例有所增加。相比之下,已鉴定出相对较小的PT和PRN序列多态性,但未发现与疫苗接种计划有明显关联。PRN吸附于铝盐似乎对小鼠百日咳肺部攻击试验中的最佳保护能力至关重要。此外,临床研究表明,当PRN以8微克剂量吸附时,抗PRN抗体水平高于以3微克剂量未吸附的PRN。因此,现有数据表明,适当配方的含PT和PRN的无细胞疫苗是百日咳免疫的首选。

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