Leite Daniela, Camargo Carlos Henrique, Kashino Suely Sanae, Polatto Ricardo, Martins Luciano Moura, Pereira Juliana Cristina, Pawloski Lucia, Tondella Maria Lucia, Oliveira Rosangela Siqueira de, Vaz de Lima Lourdes Rehder de Andrade
Department of Bacteriology, National Reference Laboratory for Pertussis, Instituto Adolfo Lutz, São Paulo, Brazil.
Department of Immunology, Instituto Adolfo Lutz, São Paulo, Brazil.
Vaccine X. 2021 Jun 7;8:100103. doi: 10.1016/j.jvacx.2021.100103. eCollection 2021 Aug.
Many countries have reported antigenic divergence among circulating strains, mainly in those countries which introduced the acellular pertussis (aP) vaccine. This phenomenon can be seen, for example, with the recent rise of pertactin (Prn)-deficient strains, one of the antigens included in aP vaccine formulas. The whole cell pertussis (wP) vaccine has been used in Brazil since 1977 for the primary pertussis, diphtheria and tetanus immunization series. In 2014, the aP vaccine was recommended for women during pregnancy to protect infants in the first months of life. Our objective was to determine the prevalence of Prn-deficiency in 511 isolates of collected in Brazil during 2010-2016. All isolates were characterized, through PFGE and serotyping, and screened for the loss of Prn by ELISA. Prn-deficiency was confirmed by immunoblotting, and identification of the possible genetic markers was performed with PCR and Sanger sequencing. Results indicate that 110 PFGE profiles are currently circulating, with five profiles representing the majority, and the predominant serotype 3, has been gradually replaced by serotype 2 and serotype 2,3. ELISA screening and immunoblotting identified three Prn-deficient isolates. Genotypic characterization by PCR and sequencing indicated that one isolate had a promoter mutation in while the other two did not have an obvious genetic explanation for their deficiency. While the lack of Prn was identified in a few isolates, this study did not detect a relevant occurrence of Prn-deficiency, until 2016, confirming previous observations that Prn-deficiency is likely aP vaccine-driven.
许多国家都报告了流行菌株之间的抗原性差异,主要发生在那些引入了无细胞百日咳(aP)疫苗的国家。例如,随着百日咳杆菌黏附素(Prn)缺陷菌株的近期增多,这种现象就可以被观察到,Prn是aP疫苗配方中包含的抗原之一。自1977年以来,全细胞百日咳(wP)疫苗一直在巴西用于百日咳、白喉和破伤风的初次免疫接种系列。2014年,建议孕妇接种aP疫苗,以保护出生后最初几个月的婴儿。我们的目标是确定2010年至2016年期间在巴西收集的511株分离株中Prn缺陷的流行情况。通过脉冲场凝胶电泳(PFGE)和血清分型对所有分离株进行特征分析,并通过酶联免疫吸附测定(ELISA)筛选Prn的缺失情况。通过免疫印迹法确认Prn缺陷,并使用聚合酶链反应(PCR)和桑格测序法鉴定可能的基因标记。结果表明,目前有110种PFGE图谱在流行,其中5种图谱占大多数,主要血清型3已逐渐被血清型2和血清型2,3所取代。ELISA筛选和免疫印迹法鉴定出3株Prn缺陷分离株。通过PCR和测序进行的基因分型表明,1株分离株在[具体基因名称]中有启动子突变,而另外2株分离株的缺陷没有明显的遗传学解释。虽然在少数分离株中发现了Prn的缺失,但本研究在2016年之前未检测到Prn缺陷的相关发生情况,证实了先前的观察结果,即Prn缺陷可能是由aP疫苗驱动的。