Institut Pasteur, Université Paris Cité, Inserm UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
Diaccurate SA, Paris, France.
JCI Insight. 2023 Jul 10;8(13):e166602. doi: 10.1172/jci.insight.166602.
SARS-CoV-2 mRNA vaccination generates protective B cell responses targeting the SARS-CoV-2 spike glycoprotein. Whereas anti-spike memory B cell responses are long lasting, the anti-spike humoral antibody response progressively wanes, making booster vaccinations necessary for maintaining protective immunity. Here, we qualitatively investigated the plasmablast responses by measuring from single cells within hours of sampling the affinity of their secreted antibody for the SARS-CoV-2 spike receptor binding domain (RBD) in cohorts of BNT162b2-vaccinated naive and COVID-19-recovered individuals. Using a droplet microfluidic and imaging approach, we analyzed more than 4,000 single IgG-secreting cells, revealing high interindividual variability in affinity for RBD, with variations over 4 logs. High-affinity plasmablasts were induced by BNT162b2 vaccination against Hu-1 and Omicron RBD but disappeared quickly thereafter, whereas low-affinity plasmablasts represented more than 65% of the plasmablast response at all time points. Our droplet-based method thus proves efficient at fast and qualitative immune monitoring and should be helpful for optimization of vaccination protocols.
SARS-CoV-2 mRNA 疫苗接种可产生针对 SARS-CoV-2 刺突糖蛋白的保护性 B 细胞反应。虽然抗刺突记忆 B 细胞反应是持久的，但抗刺突体液抗体反应逐渐减弱，因此需要加强接种以维持保护性免疫。在这里，我们通过测量接种 BNT162b2 疫苗的未感染个体和 COVID-19 康复个体在采样后数小时内从单个细胞中分泌的抗体对 SARS-CoV-2 刺突受体结合域（RBD）的亲和力，定性研究了浆母细胞反应。使用液滴微流控和成像方法，我们分析了超过 4000 个单个 IgG 分泌细胞，揭示了 RBD 亲和力的个体间高度变异性，变异超过 4 个对数级。BNT162b2 疫苗接种诱导了针对 Hu-1 和奥密克戎 RBD 的高亲和力浆母细胞，但此后很快消失，而低亲和力浆母细胞在所有时间点都代表了超过 65%的浆母细胞反应。因此，我们的基于液滴的方法在快速和定性免疫监测方面非常有效，应该有助于优化疫苗接种方案。
