Institute for Laboratory Medicine and Microbiology, University Hospital of Augsburg, Augsburg, Germany.
Bundeswehr Institute of Microbiology, Munich, Germany.
Front Immunol. 2024 Aug 29;15:1423766. doi: 10.3389/fimmu.2024.1423766. eCollection 2024.
Pre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period.
Blood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics.
Spike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL‑2 (r=0.58), and spike-induced IFN‑γ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL‑2 release, and spike-induced IFN‑γ release after 6 months were significantly associated with increased IL‑2 & IL‑4, IP‑10 & MCP1, and IFN‑γ & IP‑10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00.
In summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.
先前的研究表明，冠状病毒特异性或交叉反应性 T 细胞预先存在的池在初次接种 mRNA 疫苗后，对细胞和体液免疫反应的发展有影响。然而，关于加强针接种后反应的细胞决定因素仍不完全清楚。因此，我们在健康免疫功能正常的个体中表型和功能上对刺突抗原特异性辅助性 T（Th）细胞进行了表征，并将结果与 BNT162b2 加强针接种后 6 个月内的细胞和体液免疫反应进行了相关性分析。
在 30 名健康医护人员第三次 BNT162b2 接种前、接种后 1、3 和 6 个月采集其血液。用刺突肽刺激全血，并用流式细胞术、13 plex 细胞因子测定法和基于 nCounter 的转录组学进行分析。
加强针接种后 1 个月时的刺突特异性 IgG 水平与预先存在的 CD154+CD69+IFN-γ+CD4+效应记忆细胞以及刺突诱导的 IL-2 和 IL-17A 分泌相关。早期（1 个月）的加强针后刺突 IgG 水平（r=0.49）、刺突诱导的 IL-2（r=0.58）和刺突诱导的 IFN-γ释放（r=0.43）与各自的长期（6 个月）反应中度相关。持续的强烈 IgG 反应与加强针前 S 特异性（CD69+±CD154+±IFN-γ+）Th 细胞频率显著相关（p=0.038），尤其是双阳性/三阳性 1 型 Th 细胞。此外，6 个月时的刺突 IgG 水平、刺突诱导的 IL-2 释放和刺突诱导的 IFN-γ释放与加强针后 1 个月时的 IL-2 & IL-4、IP-10 & MCP1 和 IFN-γ & IP-10 水平升高显著相关。在转录水平上，与 T 细胞增殖和抗原呈递相关的途径的诱导表明，在加强针后 6 个月时，刺突诱导的细胞因子释放和刺突特异性 IgG 产生具有持续性。使用支持向量机模型，加强针前的刺突特异性 T 细胞频率和早期的细胞因子反应预测了加强针后 6 个月时的持续（6 个月）反应，F1 分数为 0.80-1.00。
总之，BNT162b2 加强针接种前的刺突特异性 Th 细胞和 T 细胞细胞因子特征决定了加强针后的适应性细胞和体液反应的持续时间。功能性 T 细胞检测可能有助于早期识别潜在的无反应者。
