KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway.
KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway.
EBioMedicine. 2023 Nov;97:104833. doi: 10.1016/j.ebiom.2023.104833. Epub 2023 Oct 14.
Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection.
We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3-4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors.
After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5-6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses.
Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population.
CEPI and internal funds.
肾移植受者（KTR）患严重 COVID-19 的风险很高，且对疫苗接种的反应不佳，因此尚不清楚连续接种疫苗是否能提供免疫保护。
我们进行了一项血清学指导的干预性研究，对未能产生血清转化的 KTR 患者进行了复种，并监测了挪威疫苗接种计划后 KTR 的血清转化情况。我们分析了第 2 剂（n=432）至第 6 剂（n=37）mRNA 疫苗后 IgG 抗 RBD 刺突反应。在干预队列中，在接种 3-4 剂疫苗后（n=30）评估了 Spike 特异性 T 和 B 细胞反应的频率和表型。此外，我们评估了突破性感染（n=32）的特异性 T 和 B 细胞反应，测量了炎症细胞因子和广谱交叉中和抗体，并定义了 COVID-19 相关住院和死亡的发生率。挪威 KTR 队列以男性为主（2323 名男性，1297 名女性），共采集了 114 名男性和 78 名女性供者的 PBMC。
接种第 3 剂疫苗后，大多数 KTR 产生了 Spike 特异性 T 细胞反应，但 Spike 结合 B 细胞明显减少，且记忆细胞较少。B 细胞反应包括一个可以结合 Omicron VOC 的交叉反应亚群，该亚群在突破性感染（BTI）后扩增，并产生记忆 IgG B 细胞反应。在 BTI 后，KTR 出现了更多的 Spike 特异性 T 细胞、新出现的非 Spike T 和 B 细胞反应以及全身性炎症特征。晚些时候在接种第 5-6 剂后出现血清转化，但 38%（14/37）的 KTR 即使接种了多剂疫苗也无法检测到免疫。
加强疫苗接种可以诱导 Spike 特异性免疫，这种免疫在突破性感染中可能会扩大，这突显了疫苗接种对保护这一脆弱人群的益处。
CEPI 和内部资金。
