INGM, Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
INGM, Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Clin Immunol. 2024 Apr;261:110164. doi: 10.1016/j.clim.2024.110164. Epub 2024 Feb 28.
Multiple vaccines have been approved to control COVID-19 pandemic, with Pfizer/BioNTech (BNT162b2) being widely used. We conducted a longitudinal analysis of the immune response elicited after three doses of the BNT162b2 vaccine in individuals who have previously experienced SARS-CoV-2 infection and in unexperienced ones. We conducted immunological analyses and single-cell transcriptomics of circulating T and B lymphocytes, combined to CITE-seq or LIBRA-seq, and VDJ-seq. We found that antibody levels against SARS-CoV-2 Spike, NTD and RBD from wild-type, delta and omicron VoCs show comparable dynamics in both vaccination groups, with a peak after the second dose, a decline after six months and a restoration after the booster dose. The antibody neutralization activity was maintained, with lower titers against the omicron variant. Spike-specific memory B cell response was sustained over the vaccination schedule. Clonal analysis revealed that Spike-specific B cells were polyclonal, with a partial clone conservation from natural infection to vaccination. Spike-specific T cell responses were oriented towards effector and effector memory phenotypes, with similar trends in unexperienced and experienced individuals. The CD8 T cell compartment showed a higher clonal expansion and persistence than CD4 T cells. The first two vaccinations doses tended to induce new clones rather than promoting expansion of pre-existing clones. However, we identified a fraction of Spike-specific CD8 T cell clones persisting from natural infection that were boosted by vaccination and clones specifically induced by vaccination. Collectively, our observations revealed a moderate effect of the second dose in enhancing the immune responses elicited after the first vaccination. Differently, we found that a third dose was necessary to restore comparable levels of neutralizing antibodies and Spike-specific T and B cell responses in individuals who experienced a natural SARS-CoV-2 infection.
多种疫苗已被批准用于控制 COVID-19 大流行，其中辉瑞/生物技术公司（BNT162b2）被广泛使用。我们对先前感染过 SARS-CoV-2 且未感染过 SARS-CoV-2 的个体接种三剂 BNT162b2 疫苗后产生的免疫反应进行了纵向分析。我们对循环 T 和 B 淋巴细胞进行了免疫分析和单细胞转录组学分析，结合 CITE-seq 或 LIBRA-seq 和 VDJ-seq。我们发现，针对野生型、delta 和 omicron VoCs 的 SARS-CoV-2 刺突、NTD 和 RBD 的抗体水平在两组接种者中表现出相似的动态，在第二剂后达到峰值，六个月后下降，加强剂后恢复。抗体中和活性得以维持，对 omicron 变体的滴度较低。Spike 特异性记忆 B 细胞反应在整个接种计划中持续存在。克隆分析显示，Spike 特异性 B 细胞呈多克隆性，从自然感染到接种疫苗存在部分克隆保守性。Spike 特异性 T 细胞反应倾向于效应和效应记忆表型，在未感染和感染个体中存在相似的趋势。CD8 T 细胞区室的克隆扩增和持续存在高于 CD4 T 细胞。前两剂疫苗接种倾向于诱导新的克隆，而不是促进先前存在的克隆扩增。然而，我们发现了一部分从自然感染中持续存在的 Spike 特异性 CD8 T 细胞克隆，这些克隆可被疫苗接种增强，并且可由疫苗接种特异性诱导。总的来说，我们的观察结果表明，第二剂疫苗在增强第一剂疫苗接种后产生的免疫反应方面效果适中。相反，我们发现第三剂疫苗对于恢复先前感染过 SARS-CoV-2 的个体中中和抗体和 Spike 特异性 T 和 B 细胞反应的可比水平是必要的。
