Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naïve and DENV-Exposed Individuals in a Brazilian Cohort.

Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naïve and DENV-Exposed Individuals in a Brazilian Cohort.
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DOI:
10.3389/fimmu.2022.908398
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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针对登革热病毒(DENV)的有效疫苗应诱导针对所有四种病毒血清型的平衡、持久的抗体(Ab)反应。接种后外周血中浆母细胞的爆发可能反映了疫苗特异性Ab分泌细胞的富集。在这里,我们描述了naïve和DENV暴露个体在接种减毒四价(LAT) Butantan DENV活疫苗(Butantan- dv)后的急性血浆母细胞反应。循环浆母细胞的频率是通过流式细胞术分析40名参与buantan - dv II期临床试验(NCT01696422)的参与者在接种前后(第6、12、15和22天)采集的新鲜全血样本来确定的。我们观察到DENV naïve和DENV暴露疫苗接种后第15天循环浆母细胞数量达到高峰。denv暴露的疫苗接种者经历了明显更高的等离子体扩增。在DENV-naïve疫苗接种者中,浆母细胞的持续时间比denv暴露的志愿者长约三周。我们的研究结果表明,buantan - dv可以诱导DENV-naïve和DENV暴露个体的浆母细胞反应,并证明了先前存在的DENV免疫对buantan - dv诱导的b细胞反应的影响。
An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naïve and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naïve and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naïve vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naïve and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.
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