Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China; Institute of Viruses and Infectious Diseases, Nanjing University, Jiangsu, China.
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China; Institute of Viruses and Infectious Diseases, Nanjing University, Jiangsu, China.
Clin Microbiol Infect. 2022 Mar;28(3):410-418. doi: 10.1016/j.cmi.2021.10.006. Epub 2021 Oct 26.
The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive.
In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4 and CD8 T cells and their memory subsets were simultaneously measured in this cohort.
SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4 T cells (0.57%, 0.47-0.66%) and CD8 T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51-0.75%) of CD4 T cells and 0.47% (0.38-0.58%) of CD8 T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4 T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8 T cells (r 0.48, p <0.0001).
CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.
科兴新冠病毒灭活疫苗诱导的动态适应性免疫反应仍不清楚。
在一项前瞻性队列研究中，100 名对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）无免疫力的医疗保健专业人员接受了两剂科兴疫苗，我们在四个不同时间点分析了 SARS-CoV-2 特异性体液和细胞反应，包括接种前（T1）、第一剂后 2 周（T2）、加强针后 2 周（T3）和加强针后 8-10 周（T4）。在该队列中同时测量了 SARS-CoV-2 特异性抗体、血清中和活性、外周 B 细胞、CD4 和 CD8 T 细胞及其记忆亚群。
两剂后，SARS-CoV-2 刺突特异性 IgG 反应达到峰值（几何平均滴度（GMT）54827，30969-97065），并在 T4 时迅速下降（GMT 502，212-1190），而检测到亚最佳 IgA 反应（GMT 5，2-9）。T3 时有效诱导了刺突特异性循环 B 细胞（占总 B 细胞的 0.60%，0.46-0.73%）和记忆 B 细胞（占总记忆 B 细胞的 1.18%，0.92-1.67%），并持续存在（0.33%，0.23-0.43%；0.87%，0.05-1.67%，分别）。在 T3 时检测到 SARS-CoV-2 特异性循环 CD4 T 细胞（0.57%，0.47-0.66%）和 CD8 T 细胞（1.29%，1.04-1.54%）。在 T4 时，0.78%（0.43-1.20%）的记忆 CD4+T 细胞和 0.68%（0.29-1.30%）的记忆 CD8+T 细胞被鉴定为 SARS-CoV-2 特异性，而 0.62%（0.51-0.75%）的 CD4 T 细胞和 0.47%（0.38-0.58%）的 CD8 T 细胞为 SARS-CoV-2 特异性终末分化效应记忆细胞。此外，年龄和剂量间隔影响科兴疫苗诱导的免疫反应的大小。SARS-CoV-2 记忆 CD4 T 细胞与受体结合域（RBD）特异性记忆 B 细胞（r 0.87，p<0.0001）和 SARS-CoV-2 特异性记忆 CD8 T 细胞（r 0.48，p<0.0001）强烈相关。
科兴疫苗诱导了强烈的循环和记忆 B 细胞和 T 细胞反应。我们的研究为人类灭活病毒疫苗的潜在免疫生物学提供了新的见解，并可能对未来的疫苗策略产生影响。
