与人类接种乙型肝炎疫苗接种后的全身反应原性相关的炎症

StephenW

Vaccine. 2019 Mar 5. pii: S0264-410X(19)30209-9. doi: 10.1016/j.vaccine.2019.02.015. [Epub ahead of print]
Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans.
Burny W1, Marchant A2, Hervé C3, Callegaro A3, Caubet M3, Fissette L3, Gheyle L4, Legrand C5, Ndour C5, Tavares Da Silva F3, van der Most R3, Willems F2, Didierlaurent AM3, Yarzabal J3; ECR-008 study group.
Author information

1
    GSK, Rixensart/Wavre, Belgium. Electronic address: [email protected].
2
    Institute for Medical Immunology, Université libre de Bruxelles, Charleroi, Belgium.
3
    GSK, Rixensart/Wavre, Belgium.
4
    SGS Life Science Services, Antwerp, Belgium.
5
    Institute of Statistics, Biostatistics and Actuarial Sciences (ISBA), Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Abstract
BACKGROUND:

Adjuvants like AS01B increase the immunogenicity of vaccines and generally cause increased transient reactogenicity compared with Alum. A phase II randomized trial was conducted to characterize the response to AS01B 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 B-naïve adults aged 18-45 years randomized 1:1 to receive either two doses of HBsAg-AS01B 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 AS01B induced higher HBsAg-specific antibody levels than Alum. Local and systemic symptoms were more frequent in individuals who received HBsAg AS01B/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 AS01B but not after Alum or placebo. Lymphocyte counts decreased in the AS01B 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-AS01B or HBsAg-Alum immunization. Following the second vaccine dose, CRP, IL-6, IP-10, IFN-γ, MIP-1β 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-γ signals were associated with systemic reactogenicity following administration of AS01B-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.
TRIAL REGISTRATION:

www.clinicaltrials.gov NCT01777295.

Copyright © 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.
KEYWORDS:

Association with systemic symptoms; HBsAg-AS01B adjuvanted vaccine; IFNγ signals; IL-6 signals; Innate response; Reactogenicity

PMID:
    30850240
DOI:
    10.1016/j.vaccine.2019.02.015

StephenW

疫苗。 2019年3月5日.pii：S0264-410X（19）30209-9。 doi：10.1016 / j.vaccine.2019.02.015。 [印刷前的电子版]
与人类接种乙型肝炎疫苗接种后的全身反应原性相关的炎症参数。
Burny W1，Marchant A2，HervéC3，Callegaro A3，Caubet M3，Fissette L3，Gheyle L4，Legrand C5，Ndour C5，Tavares Da Silva F3，van der Most R3，Willems F2，Didierlaurent AM3，Yarzabal J3; ECR-008研究组。
作者信息

1
GSK，Rixensart / Wavre，比利时。电子地址：[email protected]。
2
比利时沙勒罗瓦布鲁塞尔自由大学医学免疫学研究所。
3
GSK，Rixensart / Wavre，比利时。
4
比利时安特卫普SGS生命科学服务中心。
五
比利时Louvain-la-Neuve，Louvain天主教大学统计学，生物统计学和精算学（ISBA）。

抽象
背景：

像AS01B这样的佐剂增加了疫苗的免疫原性，并且与明矾相比通常会导致瞬时反应原性增加。进行了II期随机试验以表征对AS01B和明矾佐剂疫苗的反应。进行事后分析以检查反应原性与先天免疫参数之间的关联。
方法：

该试验涉及60名未接受过乙型肝炎的18-45岁成人，随机1：1在第（D）0和D30天接受两剂HBsAg-AS01B，或在D0，D30，D180接受三剂HBsAg-Alum。在疫苗接种之前，所有受试者都接受安慰剂注射以区分注射过程和疫苗接种的影响。主要结果包括疫苗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。使用线性回归探索关联。
发现：

含有AS01B的疫苗诱导的HBsAg特异性抗体水平高于明矾。接受HBsAg AS01B /明矾疫苗或安慰剂的患者出现局部和全身症状较为频繁，但症状轻微且寿命短。在第一次HBsAg-AS01B或HBsAg-明矾免疫后，C-反应蛋白（CRP）bili bili bili bili bili bili bili bili bili IL-6的血液水平。在第二次疫苗剂量后，CRP，IL-6，IP-10，IFN-γ，MIP-1β和MCP-2被鉴定为与系统性相关的关键参数。这些观察结果使用从先前研究中提取的独立数据集确认。对HBsAg佐剂疫苗的免疫应答（NCT00805389）。
结论：

施用AS01B佐剂疫苗后，IL-6和IFN-γ信号与全身反应原性相关。这些信号类似于先前与HBsAg佐剂疫苗诱导的抗体和T细胞应答相关的信号，表明类似的先天免疫信号可能具有辅助反应原性和免疫原性。
试用注册：

www.clinicaltrials.gov NCT01777295。

版权所有©2019 GlaxoSmithKline Biologicals SA。由Elsevier Ltd发布。保留所有权利。
关键词：

与全身症状相关; HBsAg-AS01B佐剂疫苗; IFNγ信号; IL-6信号;先天的反应;反应力

结论：
30850240
DOI：
10.1016 / j.vaccine.2019.02.015

StephenW

https://www.sciencedirect.com/sc ... 19302099?via%3Dihub