Song Xinran, Chen Weixin, Bai Shuang, Lv Min, Wang Jian, Zhang Ao, Wu Jiang, Zhao Wei
Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, China.
Beijing Research Center for Respiratory Infectious Diseases, Beijing, China.
Front Immunol. 2025 Jul 17;16:1636629. doi: 10.3389/fimmu.2025.1636629. eCollection 2025.
Inactivated COVID-19 vaccines exhibit more rapid declines in antibody levels than other vaccine platforms, likely owing to transient antigen exposure and limited germinal center persistence. Moreover, although homologous boosting effectively restores humoral immunity, concerns persist regarding potential T cell exhaustion with repeated antigen exposure. We evaluated the effectiveness of delayed homologous CoronaVac booster immunization in reactivating immune memory.
A prospective longitudinal cohort study was conducted with 83 healthy adults who received two CoronaVac vaccine doses (14-day interval) and a homologous booster shot after 12 months. Peripheral blood samples were collected 0, 3, 7, 10, and 14 days after booster vaccination. Neutralizing antibodies were analysed using live-virus microneutralization assays. Anti-receptor-binding domain immunoglobulin subclasses (IgG1, IgG2, IgG3, IgG4) were detected using enzyme-linked immunosorbent assay. Cytokine secretion (interferon [IFN]-γ/interleukin [IL]-2/IL-4/IL-5) was assessed using enzyme-linked immunospot assay. T cell polarization and exhaustion markers (T-bet/GATA3 and CD69/CTLA-4/PD-1) were evaluated using flow cytometry.
The geometric mean titer of neutralizing antibodies reached 254.5 on day 14. The initial immune response was dominated by IgG3, which subsequently shifted to IgG1. A significant Th1-type cellular immune response was characterized by increased IFN-γ and IL-2 secretion, and upregulated T-bet expression. Transient CD69+ T cell activation occurred between days 3 and 10 without sustained PD-1 and CTLA-4 elevation.
Delayed homologous CoronaVac booster immunization effectively reactivates immune memory, facilitated by Th1 polarization and transient T cell activation, which do not result in T cell exhaustion. These findings suggest the potential application of long-interval immunization strategies against COVID-19.
与其他疫苗平台相比，灭活新冠病毒疫苗的抗体水平下降更快，这可能是由于抗原短暂暴露和生发中心持久性有限所致。此外，尽管同源加强免疫能有效恢复体液免疫，但人们仍担心反复抗原暴露可能导致T细胞耗竭。我们评估了延迟同源 CoronaVac 加强免疫激活免疫记忆的有效性。
对83名健康成年人进行了一项前瞻性纵向队列研究，这些成年人接受了两剂 CoronaVac 疫苗（间隔14天），并在12个月后接受了同源加强注射。在加强疫苗接种后的0、3、7、10和14天采集外周血样本。使用活病毒微量中和试验分析中和抗体。使用酶联免疫吸附试验检测抗受体结合域免疫球蛋白亚类（IgG1、IgG2、IgG3、IgG4）。使用酶联免疫斑点试验评估细胞因子分泌（干扰素[IFN]-γ/白细胞介素[IL]-2/IL-4/IL-5）。使用流式细胞术评估T细胞极化和耗竭标志物（T-bet/GATA3和CD69/CTLA-4/PD-1）。
中和抗体的几何平均滴度在第14天达到254.5。初始免疫反应以IgG3为主，随后转变为IgG1。显著的Th1型细胞免疫反应的特征是IFN-γ和IL-2分泌增加以及T-bet表达上调。在第3天至第10天之间发生了短暂的CD69+T细胞激活，而PD-1和CTLA-4没有持续升高。
延迟同源CoronaVac加强免疫有效地激活了免疫记忆，这得益于Th1极化和短暂的T细胞激活，且不会导致T细胞耗竭。这些发现提示了长间隔免疫策略在对抗新冠病毒方面的潜在应用。
