Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells.

Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells.
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DOI:
10.1093/infdis/jis212
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发表时间:
2012-05-01
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Pollard AJ
Pollard AJ
中科院分区:
其他
文献类型:
--
作者:
Clutterbuck EA;Lazarus R;Yu LM;Bowman J;Bateman EA;Diggle L;Angus B;Peto TE;Beverley PC;Mant D;Pollard AJ

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背景:23价非结合肺炎球菌多糖疫苗(23vP),常规在65岁时接种,效果有限,再接种可诱导减弱的抗体应答。 目前尚不清楚肺炎球菌多糖蛋白结合疫苗(PCV),虽然在婴儿中非常有效,但在成人中是否比23vP提供任何免疫优势。方法:我们用PCV和23 vP联合免疫成人,研究B细胞反应,以确定PCV 7(一种7价PCV)是否在成人中诱导T依赖性反应,评估记忆B细胞在23 vP诱导的抗体低反应性中的作用,并鉴定相关的B细胞亚型。 结果:单剂量的PCV 7诱导外周血中特定类型记忆B细胞群的显著增加,表明T依赖性应答。 相反,23vP免疫导致记忆B细胞频率下降。此外,当在23vP后给予时,对随后用PCV 7免疫的记忆B细胞应答减弱。值得注意的是,B1b细胞,在保护小鼠免受肺炎球菌感染方面很重要的一个亚群,在人体中用23 vP免疫后也被耗尽。结论:本研究表明,在成人中,PCV 7可能比23 vP具有免疫优势,23 vP诱导的记忆和B1b细胞亚群的耗竭可能为抗体低反应性和23 vP的有限有效性提供了基础。 临床试验注册。ISRCTN:78768849。
Background. A 23-valent unconjugated pneumococcal polysaccharide vaccine (23vP), routinely administered at the age of 65, has limited effectiveness, and revaccination induces attenuated antibody responses. It is not known whether pneumococcal polysaccharide-protein conjugated vaccines (PCV), although highly effective in infants, offer any immunological advantages over 23vP in adults. Methods. We immunized adults with schedules combining both PCV and 23vP and investigated B-cell responses to establish whether PCV7 (a 7-valent PCV) induced T-dependent responses in adults, to assess the role of memory B cells in 23vP-induced antibody hyporesponsiveness, and to identify the B-cell subtypes involved. Results. A single dose of PCV7 induced significant increases in serotype-specific memory B-cell populations in peripheral blood indicating a T-dependent response. Conversely, immunization with 23vP resulted in a decrease in memory B-cell frequency. Furthermore, memory B-cell responses to subsequent immunization with PCV7, when given after 23vP, were attenuated. Notably, B1b cells, a subset important in protecting mice against pneumococci, were also depleted following immunization with 23vP in humans. Conclusions. This study indicates that PCV7 may have an immunological advantage over 23vP in adults and that 23vP-induced depletion of memory and B1b-cell subsets may provide a basis for antibody hyporesponsiveness and the limited effectiveness of 23vP. Clinical Trials Registration. ISRCTN: 78768849.
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发表时间: 1985-01-01
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