In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4⁺ and CD8⁺ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4⁺ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8⁺ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8⁺ T-cell response in previously infected individuals.

在这项研究中，对来自五个不同组的外周血单核细胞进行了抗体反应和单细胞 RNA-seq 分析：接种 AZD1222 (AZ) 或 Ad5-nCoV (Cso) 的初始受试者、先前感染但后来接种的个体 (混合型）与 AZD1222 (AZ-hb) 或 Ad5-nCoV (Cso-hb)，以及那些感染了 COVID-19 (Inf) 并已康复的人。结果表明，AZ 比 Cso 诱导更强烈的中和抗体反应。单细胞 RNA 数据显示 Cso 和 Cso-hb 中存在高频率的记忆 B 细胞。相反，AZ 和 AZ-hb 组表现出表达CXCR4的活化幼稚 B 细胞比例最高。 CD4 ⁺和 CD8 ⁺ T 细胞的转录组分析表明，疫苗接种、混合免疫或自然感染后存在异质反应。然而，单剂量的 Ad5-nCoV 足以强烈激活表达ANX1和FOS的 CD4 ⁺ T 细胞（幼稚细胞和记忆细胞），类似于 AZ 观察到的混合反应。一个有趣的发现是Cso-hb 组中表达GZMB、GZMH和IFNG基因的 CD8 ⁺ T 细胞子集的强烈激活。我们的研究结果表明，两种疫苗都能有效刺激细胞免疫反应。然而，Ad5-nCoV 在先前感染的个体中诱导了更强烈的 CD8 ⁺ T 细胞反应。