Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever.

Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever.
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Vi-疫苗接种可诱导与伤寒保护相关的异质浆细胞反应。

DOI:
10.3389/fimmu.2020.574057
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发表时间:
2020
影响因子:
7.3
通讯作者:
Pollard AJ
Pollard AJ
中科院分区:
医学2区
文献类型:
--
作者:
Cross DL;Verheul MK;Leipold MD;Obermoser G;Jin C;Jones E;Starr JS;Mohorianu I;Blohmke CJ;Maecker HT;Napolitani G;Hill J;Pollard AJ

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Vi-多糖结合疫苗对伤寒病例有效;然而,保护的绝对相关性尚未建立。在这项研究中,我们研究了随后接受伤寒沙门氏菌攻击的健康成年人对 Vi-破伤风类毒素结合疫苗 (Vi-TT) 和普通多糖疫苗 (Vi-PS) 的白细胞反应。通过质谱流式细胞术和 Vi-ELISpot 测定评估免疫反应及其与攻击结果的关联。两种疫苗中的免疫均诱导浆细胞显着扩增,仅在 Vi-TT 后即可检测到适度的滤泡辅助 T 细胞反应。 Vi-TT 接受者中 Vi 特异性 IgG 和 IgM B 细胞反应的幅度要大得多。有趣的是,在两个疫苗组中都观察到表达粘膜迁移标记物 α4β7 和 CCR10 的 IgA+ 浆细胞子集显着增加,这表明 Vi 疫苗接种诱导了肠向性粘膜反应。总浆细胞反应与 Vi-TT 疫苗接种者对伤寒的保护显着相关,但与 Vi-PS 无关。尽管 Vi-PS 存在趋势,但 IgA+ 浆细胞与任一疫苗的保护作用均无显着相关性。相反,浆细胞反应的 IgA- 部分仅与 Vi-TT 中的保护相关。总之,这些数据表明,包括肠道归巢细胞和全身抗体分泌细胞在内的表型异质反应可能对于 Vi-TT 疫苗接种诱导的保护至关重要。
Vi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vaccine (Vi-PS) in healthy adults subsequently challenged with Salmonella Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot assay. Immunization induced significant expansion of plasma cells in both vaccines with modest T follicular helper cell responses detectable after Vi-TT only. The Vi-specific IgG and IgM B cell response was considerably greater in magnitude in Vi-TT recipients. Intriguingly, a significant increase in a subset of IgA+ plasma cells expressing mucosal migratory markers α4β7 and CCR10 was observed in both vaccine groups, suggesting a gut-tropic, mucosal response is induced by Vi-vaccination. The total plasma cell response was significantly associated with protection against typhoid fever in Vi-TT vaccinees but not Vi-PS. IgA+ plasma cells were not significantly associated with protection for either vaccine, although a trend is seen for Vi-PS. Conversely, the IgA- fraction of the plasma cell response was only associated with protection in Vi-TT. In summary, these data indicate that a phenotypically heterogeneous response including both gut-homing and systemic antibody secreting cells may be critical for protection induced by Vi-TT vaccination.
DOI: 10.1093/infdis/jis212
发表时间: 2012-05-01
期刊: The Journal of infectious diseases
影响因子: --
作者:
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影响因子: 7.3
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DOI: 10.1016/s1074-7613(02)00289-3
发表时间: 2002-03-01
期刊: IMMUNITY
影响因子: 32.4
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