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对3.5岁儿童接种PCV-7或PCV-13后再接种PCV-13加强针的记忆B细胞反应。

Memory B cell response to a PCV-13 booster in 3.5year old children primed with either PCV-7 or PCV-13.

作者信息

Trück Johannes, Thompson Amber, Morales-Aza Begonia, Clutterbuck Elizabeth A, Voysey Merryn, Clarke Ed, Snape Matthew D, Kelly Dominic F, Finn Adam, Pollard Andrew J

机构信息

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.

出版信息

Vaccine. 2017 May 9;35(20):2701-2708. doi: 10.1016/j.vaccine.2017.03.079. Epub 2017 Apr 6.

Abstract

Pneumococcal protein-polysaccharide conjugate vaccines provide direct protection against Streptococcus pneumoniae through the induction of persistent anti-polysaccharide antibodies, and by priming for a rapid secondary antibody response. Memory B cells (B) generated during an initial immune response are responsible for both the more rapid and quantitatively greater secondary antibody response and are also thought to contribute to the ongoing production of plasma cells providing long-term antibody persistence. We recruited 3.5-year-old children who had participated in a previous clinical trial comparing infant immunization with either a 7-valent (PCV-7) or a 13-valent pneumococcal conjugate vaccine (PCV-13) to investigate whether prior priming with pneumococcal antigens influences B responses. Blood was taken before and 1month after a PCV-13 booster. B were quantified using a cultured ELISpot assay for pneumococcal serotypes 1, 3, 4, 14, 19A, 23F, and with diphtheria and tetanus toxoid as controls, and then correlated with serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers. In total, blood samples from 62 participants were available for analysis. Serotype-specific B frequencies were generally low at baseline (before boost) although for serotypes 14 and 3, they were significantly higher in children primed with PCV-13 than PCV-7 primed children. Following the PCV-13 booster, B frequencies increased and were not different between the groups for all serotypes. A strong inverse correlation was found between antibody concentrations and OPA titers at baseline and B following booster vaccination for serotype 3 but not for other serotypes suggesting that, for this serotype, pre-existing serotype-specific antibodies may inhibit B formation in response to vaccination. Clinicaltrials.gov registration number: NCT01095471.

摘要

肺炎球菌蛋白-多糖结合疫苗通过诱导持续的抗多糖抗体以及引发快速的二次抗体反应,为抵御肺炎链球菌提供直接保护。初次免疫反应期间产生的记忆B细胞(B细胞)负责更快速且数量上更多的二次抗体反应,并且也被认为有助于浆细胞的持续产生,从而提供长期的抗体持久性。我们招募了参与过一项先前临床试验的3.5岁儿童,该试验比较了婴儿接种7价(PCV-7)或13价肺炎球菌结合疫苗(PCV-13)的情况,以研究先前用肺炎球菌抗原进行的致敏是否会影响B细胞反应。在接种PCV-13加强针之前和之后1个月采集血液。使用针对肺炎球菌血清型1、3、4、14、19A、23F的培养ELISpot测定法对B细胞进行定量,并以白喉和破伤风类毒素作为对照,然后将其与血清型特异性IgG浓度和调理吞噬活性(OPA)滴度相关联。总共62名参与者的血液样本可供分析。血清型特异性B细胞频率在基线时(加强针之前)通常较低,尽管对于血清型14和3,用PCV-13致敏的儿童中的频率显著高于用PCV-7致敏的儿童。接种PCV-13加强针后,B细胞频率增加,并且所有血清型的组间无差异。对于血清型3,在基线时抗体浓度与OPA滴度之间以及加强针接种后的B细胞之间发现了强烈的负相关,但其他血清型未发现,这表明对于该血清型,预先存在的血清型特异性抗体可能会抑制接种疫苗后B细胞的形成。Clinicaltrials.gov注册号:NCT01095471。

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