DataSheet_1_Neutralizing Antibody Activity Against the B.1.617.2 (delta) Variant Before and After a Third BNT162b2 Vaccine Dose in Hemodialysis Patients.docx

Hemodialysis patients are at high risk for severe COVID-19, and impaired seroconversion rates have been demonstrated after COVID-19 vaccination. Humoral immunity wanes over time and variants of concern with immune escape are posing an increasing threat. Little is known about protection against the B.1.617.2 (delta) variant of concern in hemodialysis patients before and after third vaccination. We determined anti-S1 IgG, surrogate neutralizing, and IgG antibodies against different SARS-CoV-2 epitopes in 84 hemodialysis patients directly before and three weeks after a third vaccine dose with BNT162b2. Third vaccination was performed after a median (IQR) of 119 (109–165) days after second vaccination. In addition, neutralizing activity against the B.1.617.2 (delta) variant was assessed in 31 seroconverted hemodialysis patients before and after third vaccination. Triple seropositivity for anti-S1 IgG, surrogate neutralizing, and anti-RBD antibodies increased from 31/84 (37%) dialysis patients after second to 80/84 (95%) after third vaccination. Neutralizing activity against the B.1.617.2 (delta) variant was significantly higher after third vaccination with a median (IQR) ID50 of 1:320 (1:160–1:1280) compared with 1:20 (0–1:40) before a third vaccine dose (P<0.001). The anti-S1 IgG index showed the strongest correlation with the ID50 against the B.1.617.2 (delta) variant determined by live virus neutralization (r=0.91). We demonstrate low neutralizing activity against the B.1.617.2 (delta) variant in dialysis patients four months after standard two-dose vaccination but a substantial increase after a third vaccine dose. Booster vaccination(s) should be considered earlier than 6 months after the second vaccine dose in immunocompromised individuals.

血液透析患者罹患重症新型冠状病毒肺炎（Corona Virus Disease 2019, COVID-19）的风险极高，且已有研究证实，接种COVID-19疫苗后该人群的血清转换率受损。体液免疫随时间推移逐渐衰减，而具备免疫逃逸能力的关切变异株（Variant of Concern, VoC）正构成日益严峻的威胁。目前对于血液透析患者在第三次疫苗接种前后针对B.1.617.2（德尔塔，Delta）关切变异株的保护效果所知甚少。
本研究检测了84名血液透析患者在接受BNT162b2第三次疫苗接种前即刻及接种后三周时的抗S1 IgG、替代中和抗体以及针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）不同表位的IgG抗体水平。第三次疫苗接种的实施时间为第二次疫苗接种后的中位（四分位间距，IQR）119天（109~165天）。
此外，本研究还评估了31名已发生血清转换的血液透析患者在第三次疫苗接种前后针对B.1.617.2（德尔塔）变异株的中和活性。抗S1 IgG、替代中和抗体及抗受体结合域（Receptor Binding Domain, RBD）抗体的三重血清阳性率从第二次疫苗接种后的31/84（37%）提升至第三次疫苗接种后的80/84（95%）。第三次疫苗接种后，患者针对B.1.617.2（德尔塔）变异株的中和活性显著升高，其中位半数抑制滴度（ID50）为1:320（1:160~1:1280），而第三次疫苗接种前的中位ID50仅为1:20（0~1:40）（P<0.001）。抗S1 IgG指数与通过活病毒中和试验测得的针对B.1.617.2（德尔塔）变异株的ID50呈现最强相关性（r=0.91）。
本研究证实，接受标准两剂次疫苗接种四个月后的血液透析患者，其针对B.1.617.2（德尔塔）变异株的中和活性较低，但在第三次疫苗接种后该活性可出现显著提升。免疫功能低下人群应考虑在第二剂疫苗接种后6个月内提前开展加强疫苗接种。