PDF(Pubmed)
Abstract：
Preventing SARS-CoV-2 infection is of utmost importance in allogeneic hematopoietic cell transplantation patients (allo-HCT), given their heightened susceptibility to adverse outcomes associated with SARS-CoV-2 infection. However, limited data are available regarding the immune response to COVID-19 vaccines in these subjects, particularly concerning the generation and persistence of spike-specific memory response. Here, we analyzed the spike-specific memory B cells in a cohort of allo-HCT recipients vaccinated with multiple doses of the mRNA-1273 vaccine and monitored the spike-specific antibody response from baseline up to one month after the fourth dose. After the primary vaccine series, the frequency of spike-specific B cells, detected within the pool of Ig-switched CD19+ cells, significantly increased. The booster dose further induced a significant expansion, reaching up to 0.28% of spike-specific B cells. The kinetics of this expansion were slower in the allo-HCT recipients compared to healthy controls. Spike-specific IgG and ACE2/RBD binding inhibition activity were observed in 80% of the allo-HCT recipients after the first two doses, with a significant increase after the third and fourth booster doses, including in the subjects who did not respond to the primary vaccine series. Additionally, 87% of the allo-HCT recipients exhibited positive cross-inhibition activity against the BA.1 variant. Our findings provide evidence that allo-HCT recipients need repeated doses of the mRNA-1273 vaccine to induceSARS-CoV-2 specific immune response similar to that observed in healthy individuals. This is particularly crucial for vulnerable individuals who may exhibit a limited response to the primary series of SARS-CoV-2 vaccination.
摘要：
预防SARS-CoV-2感染在异基因造血细胞移植患者（allo-HCT）中至关重要，鉴于他们对与SARS-CoV-2感染相关的不良结局的易感性更高。然而,关于这些受试者对COVID-19疫苗的免疫反应的数据有限，特别是关于尖峰特异性记忆反应的产生和持续。这里,我们分析了一组接受多剂量mRNA-1273疫苗疫苗接种的allo-HCT受者中的尖峰特异性记忆B细胞,并在第四剂疫苗接种后1个月内从基线监测尖峰特异性抗体应答.在初级疫苗系列之后，尖峰特异性B细胞的频率，在Ig交换CD19+细胞池中检测到，显著增加。加强剂量进一步引起了显着的扩张，达到0.28%的刺突特异性B细胞。与健康对照相比,在allo-HCT接受者中这种扩增的动力学较慢。在前两个剂量后，在80％的allo-HCT接受者中观察到了尖峰特异性IgG和ACE2/RBD结合抑制活性，在第三次和第四次加强剂量后显著增加，包括对主要疫苗系列没有反应的受试者。此外,87%的allo-HCT受体表现出针对BA.1变体的阳性交叉抑制活性。我们的发现提供了证据，表明allo-HCT接受者需要重复剂量的mRNA-1273疫苗来诱导SARS-CoV-2特异性免疫反应，类似于在健康个体中观察到的免疫反应。这对于可能对主要系列SARS-CoV-2疫苗接种表现出有限反应的易受伤害个体尤其重要。
