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四价、减毒活登革热疫苗 Butantan-DV 引起的登革热病毒-naive 和登革热病毒-exposed 个体中的浆母细胞扩增：巴西队列研究。

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

机构信息

Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil.

Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, United States.

出版信息

Front Immunol. 2022 Jun 28;13:908398. doi: 10.3389/fimmu.2022.908398. eCollection 2022.

DOI:10.3389/fimmu.2022.908398
PMID:35837409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9274664/
Abstract

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.

摘要

一种有效的登革热病毒 (DENV) 疫苗应能诱导针对所有四种病毒血清型的平衡、持久的抗体 (Ab) 反应。接种疫苗后外周血中浆母细胞的爆发可能反映了富含疫苗特异性 Ab 分泌细胞。在这里，我们描述了在巴西布坦坦登革热疫苗（Butantan-DV）的活体减毒四价（LAT）疫苗接种后，来自未感染和已感染 DENV 的个体的急性浆母细胞反应。通过对 40 名参加巴西布坦坦登革热疫苗临床试验（NCT01696422）的参与者在接种前后（第 6、12、15 和 22 天）采集的新鲜全血标本进行流式细胞术分析，确定循环浆母细胞的频率。我们观察到，在接种后第 15 天，无论是在未感染 DENV 的疫苗接种者还是已感染 DENV 的疫苗接种者中，循环浆母细胞的数量都达到峰值。已感染 DENV 的疫苗接种者经历了更高的浆母细胞扩增。在未感染 DENV 的疫苗接种者中，浆母细胞的持续时间比已感染 DENV 的志愿者长约三周。我们的研究结果表明，巴西布坦坦登革热疫苗可以在未感染和已感染 DENV 的个体中诱导浆母细胞反应，并证明了预先存在的 DENV 免疫对巴西布坦坦登革热病毒诱导的 B 细胞反应的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/5308f241180b/fimmu-13-908398-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/2d6c3d4e2ec4/fimmu-13-908398-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/565a2dc4c332/fimmu-13-908398-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/fc5d2bf8459b/fimmu-13-908398-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/5308f241180b/fimmu-13-908398-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/2d6c3d4e2ec4/fimmu-13-908398-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/565a2dc4c332/fimmu-13-908398-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/fc5d2bf8459b/fimmu-13-908398-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/9274664/5308f241180b/fimmu-13-908398-g004.jpg

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