实验性百日咳全细胞疫苗在小鼠模型中的有效性。

Maciej Polak, Monika Zawadka, Ewa Mosiej, Daniel Rabczenko, Ewa Augustynowicz, Anna Lutyńska
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摘要

自20世纪90年代以来,百日咳在许多高度免疫的国家再次出现。流行百日咳分离株和疫苗株之间的遗传差异已被认为是百日咳死灰复燃的原因之一。在一些研究中观察到这种差异,以影响百日咳疫苗在小鼠模型中的有效性。在本研究中,我们利用小鼠鼻内攻击模型,评估了由属于不同PFGE组的百日咳分离株制备的四种实验性白粉病疫苗在消除四种百日咳分离株混合物引起的细菌感染方面的有效性。方法:采用PFGE V、IVγ和C组临床分离株单独或联合制备实验性白粉病疫苗。采用PFGE V、IVγ、III和C组4种分离株的混合物进行小鼠鼻内攻毒。所选择的菌株代表了目前在欧洲流行的PFGE分离株的特征(PFGE IV组和V组),波兰特有的PFGE (PFGE C组)和波兰wP疫苗的疫苗株(PFGE III组)。此外,为了研究细菌适应性,监测了在小鼠肺部感染过程中用作攻击的四种分离株的比例变化。结果和结论:所有实验性白粉病疫苗在消除小鼠肺部百日咳方面均具有相同的效果。它们的有效性不依赖于疫苗株PFGE组。在未免疫小鼠诱导的混合感染过程中,细菌适应度结果发现,PFGE IVγ组的分离物在属于PFGE III、V和c组的混合物中占主导地位。这一数据可能表明,在欧洲常见的属于PFGE IV组的分离物可能更适合在免疫力下降的条件下进行探索。
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Effectiveness of experimental whole-cell pertussis vaccines in murine model.

Introduction: Since the 1990s pertussis re-emergence has been observed in many highly immunized countries. Genetic divergence between circulating B. pertussis isolates and vaccine strains has been suggested as one of the reasons responsible for the resurgence of pertussis. This divergence was observed in some studies to affect the effectiveness of pertussis vaccine when tested in murine model. In the study, using the murine intranasal challenge model we evaluated the effectiveness of four experimental wP vaccines, prepared with B. pertussis isolates belonging to different PFGE groups, in the elimination of the bacterial infection induced with mixture of the four B. pertussis isolates.

Methods: The experimental wP vaccines were prepared with clinical isolates belonging to PFGE groups V, IVγ and C, used individually or together. The mixture of four isolates classified to PFGE groups V, IVγ, III and C was used as intranasal mice challenge. The chosen strains represent PFGE groups characteristic for isolates currently circulating in Europe (PFGE groups IV and V), specific for Poland (PFGE group C) and vaccine strains of Polish wP vaccine (PFGE group III). Additionally, to study bacterial fitness, changes in the proportions of four isolates used as the challenge within the course of infection in mice lungs were monitored.

Results and conclusions: All experimental wP vaccines were found to be equally effective in eliminating B. pertussis from mice lungs. Their effectiveness was independent on PFGE group of vaccine strain. The results on bacterial fitness during mixed infections induced in the non-immunized mice found the isolate of PFGE group IVγ dominating among the other isolates used in the mixture belonging to PFGE group III, V, and C. This data might suggest that the isolates belonging to PFGE group IV, so commonly seen in Europe, might be more fitted to explore in conditions of waning immunity.

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