Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans
Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans
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DOI：
10.1016/j.vaccine.2019.02.015
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发表时间：
2019-03-28
期刊：
影响因子：
5.5
通讯作者：
Yarzabal, Juan Pablo
中科院分区：
文献类型：
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作者：
Burny, Wivine;Marchant, Arnaud;Yarzabal, Juan Pablo
背景：与明矾相比，佐剂如AS 01（B）增加了疫苗的免疫原性，通常会导致一过性反应原性增加。进行了H期随机试验，以表征对AS 01（B）和明矾佐剂疫苗的应答。进行事后分析，以检查reactogenicity和先天性immune parameters.Methods之间的关联：该试验涉及60名肝炎13-naive成人年龄18-45岁，随机1：1接受两个剂量的HBsAg-AS 01（B）在第（D）0和D30天，或三个剂量的HBsAg-明矾在D 0，D30，D180。接种前，所有受试者均接受安慰剂注射，以区分注射过程和接种的影响。主要结局包括接种后的反应原性症状、生命体征、血液细胞因子、生化和血液学参数。使用线性regression.Findings：AS 01（B）疫苗诱导更高的HBsAg特异性抗体水平比明矾。局部和全身症状在接受HBsAg AS 01（B）/明矾疫苗或安慰剂的个体中更常见，但较轻且短暂。在AS 01（B）治疗后，C反应蛋白（CRP）、胆红素、白细胞、单核细胞和中性粒细胞计数的血液水平迅速和一过性升高，但在明矾或安慰剂治疗后未出现这种情况。明矾给药后，AS 01（B）组的淋巴细胞计数降低，乳酸脱氢酶水平降低。建模揭示了在第一次免疫接种后，全身症状与CRP和IL-6水平升高之间的相关性。在第二剂疫苗后，CRP、IL-6、IP-10、IFN-γ、MIP-1 β和MCP-2被确定为与全身症状相关的关键参数。这些观察结果使用从先前对含HBsAg佐剂的疫苗的免疫应答的研究（NCT 00805389）中提取的独立数据集来证实。结论：IL-6和IFN-γ信号与施用含AS 01（B）佐剂的疫苗后的全身反应原性相关。这些信号与先前由含Ag佐剂的疫苗诱导的抗体和T细胞应答相关的信号相似，表明相似的先天免疫信号可能是佐剂反应原性和免疫原性的基础。(C)2019年葛兰素史克生物制品有限公司爱思唯尔有限公司出版
Background: Adjuvants like AS01(B) increase the immunogenicity of vaccines and generally cause increased transient reactogenicity compared with Alum. A phase H randomized trial was conducted to characterize the response to AS01(B) and Alum adjuvanted vaccines. A post-hoc analysis was performed to examine the associations between reactogenicity and innate immune parameters.Methods: The trial involved 60 hepatitis 13-naive adults aged 18-45 years randomized 1:1 to receive either two doses of HBsAg-AS01(B) on Day (D)0 and D30, or three doses of HBsAg-Alum on D0, D30, D180. Prior to vaccination, all subjects received placebo injection in order to differentiate the impact of injection process and the vaccination. Main outcomes included reactogenicity symptoms, vital signs, blood cytokines, biochemical and hematological parameters after vaccination. Associations were explored using linear regression.Findings: The vaccine with AS01(B) induced higher HBsAg-specific antibody levels than Alum. Local and systemic symptoms were more frequent in individuals who received HBsAg AS01(B)/Alum vaccine or placebo, but were mild and short-lived. Blood levels of C-reactive protein (CRP), bilirubin, leukocyte, monocyte and neutrophil counts increased rapidly and transiently after AS01(B) but not after Alum or placebo. Lymphocyte counts decreased in the AS01(B) group and lactate dehydrogenase levels decreased after Alum. Modelling revealed associations between systemic symptoms and increased levels of CRP and IL-6 after the first HBsAg-AS01(B) or HBsAg-Alum immunization. Following the second vaccine dose, CRP, IL-6, IP-10, IFN-gamma, MIP-1 beta and MCP-2 were identified as key parameters associated with systemic symptoms. These observations were confirmed using an independent data set extracted from a previous study of the immune response to HBsAg-adjuvanted vaccines (NCT00805389).Conclusions: IL-6 and IFN-gamma signals were associated with systemic reactogenicity following administration of AS01(B)-adjuvanted vaccine. These signals were similar to those previously associated with antibody and T-cell responses induced by HBsAg-adjuvanted vaccines, suggesting that similar innate immune signals may underlie adjuvant reactogenicity and immunogenicity. (C) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.