University Health Network, Ajmera Transplant Centre, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada.
Am J Transplant. 2023 Feb;23(2):278-283. doi: 10.1016/j.ajt.2022.10.004. Epub 2023 Jan 12.
Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort.
SARS-CoV-2 刺突蛋白的突变使奥密克戎亚变体能够逃避中和抗体。在移植受者中，这种情况发生的程度尚不清楚。我们测量了 75 名主要接种疫苗的移植受者在从 BA.1 感染中康复后的 BA.4/5 交叉中和反应。在 BA.1 感染后 1 个月和 6 个月采集血清，并使用与 BA.1 和 BA.4/5 相对应的刺突构建体进行慢病毒假病毒中和测定。未感染的免疫移植受者和卫生保健工作者对照用于比较。在 BA.1 感染后，具有中和抗体反应的移植受者比例为 88.0%（66/75）针对 BA.1 和 69.3%（52/75）针对 BA.4/5（P =.005）。对 BA.4/5 的中和水平比 BA.1 低约 17 倍（IQR 10.6 至 45.1 倍，P <.0001）。BA.4/5 反应随时间而下降，并且在 6 个月时近一半的患者的反应下降≥0.5 对数（约 3 倍）。在突破 BA.1 感染的移植受者中，BA.4/5 中和抗体滴度与免疫接种的卫生保健工作者相似，但明显低于未感染的三剂接种移植受者。这些结果提供了证据，表明尽管接种疫苗和先前的奥密克戎株感染，移植受者仍面临 BA.4/5 感染的持续风险，可能需要额外的缓解策略来预防该队列的严重疾病。
