Center for Inflammation Research, VIB, Ghent, Belgium.
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
Front Immunol. 2024 Aug 14;15:1412732. doi: 10.3389/fimmu.2024.1412732. eCollection 2024.
Antibody-mediated protection can depend on mechanisms varying from neutralization to Fc-dependent innate immune-cell recruitment. Adjuvanted vaccine development relies on a holistic understanding of how adjuvants modulate the quantity/titer and quality of the antibody response.
A Phase 2 trial (ClinicalTrials.gov: NCT00805389) evaluated hepatitis B vaccines formulated with licensed adjuvants (AS01, AS01, AS03, AS04 or Alum) in antigen-naïve adults. The trial investigated the role of adjuvants in shaping antibody-effector functions, and identified an innate transcriptional response shared by AS01, AS01 and AS03. We integrated previously reported data on the innate response (gene expression, cytokine/C-reactive protein levels) and on quantitative/qualitative features of the mature antibody response (Fc-related parameters, immunoglobulin titers, avidity). Associations between the innate and humoral parameters were explored using systems vaccinology and a machine-learning framework.
A dichotomy in responses between AS01/AS03 and AS04/Alum (with the former two contributing most to the association with the humoral response) was observed across all timepoints of this longitudinal study. The consistent patterns over time suggested a similarity in the impacts of the two-dose immunization regimen, year-long interval, and non-adjuvanted antigenic challenge given one year later. An innate signature characterized by interferon pathway-related gene expression and secreted interferon-γ-induced protein 10 and C-reactive protein, which was shared by AS01 and AS03, consistently predicted both the qualitative antibody response features and the titers. The signature also predicted from the antibody response quality, the group of adjuvants from which the administered vaccine was derived.
An innate signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time.
抗体介导的保护作用可能取决于从中和到 Fc 依赖性固有免疫细胞募集等不同机制。佐剂疫苗的开发依赖于对佐剂如何调节抗体反应的数量/效价和质量的全面理解。
一项 2 期临床试验（ClinicalTrials.gov：NCT00805389）评估了在抗原初治成人中用已获许可的佐剂（AS01、AS01、AS03、AS04 或 Alum）配制的乙肝疫苗。该试验研究了佐剂在塑造抗体效应功能中的作用，并确定了 AS01、AS01 和 AS03 共有的先天转录反应。我们整合了先前关于先天反应（基因表达、细胞因子/C 反应蛋白水平）和成熟抗体反应的定量/定性特征（Fc 相关参数、免疫球蛋白滴度、亲和力）的报告数据。使用系统疫苗学和机器学习框架探索了先天和体液参数之间的关联。
在这项纵向研究的所有时间点，AS01/AS03 和 AS04/Alum 之间的反应存在二分法（前两者对与体液反应的关联贡献最大）。随着时间的推移，这些一致的模式表明，两剂免疫接种方案、一年的间隔期和一年后给予的非佐剂抗原挑战的影响相似。一个由干扰素通路相关基因表达、分泌的干扰素-γ诱导蛋白 10 和 C 反应蛋白组成的先天特征，AS01 和 AS03 共享，一致预测了定性抗体反应特征和滴度。该特征还可以根据抗体反应质量预测出所使用疫苗的佐剂组。
AS01 或 AS03 佐剂疫苗诱导的先天特征可随时间一致地预测抗体反应的幅度和质量。
