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接受维持性血液透析的患者对两剂ChAdOx1 nCoV-19疫苗接种的体液免疫反应轨迹

Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

作者信息

Ling Tsai-Chieh, Chen Po-Lin, Li Nan-Yao, Ko Wen-Chien, Sun Chien-Yao, Chao Jo-Yen, Shieh Chi-Chang, Shen Ching-Fen, Wu Jia-Ling, Huang Teng-Ching, Chao Chiao-Hsuan, Wang Jen-Ren, Chang Yu-Tzu

机构信息

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Infection Control Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Microbiol Spectr. 2023 Feb 21;11(2):e0344522. doi: 10.1128/spectrum.03445-22.

Abstract

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

摘要

ChAdOx1 nCoV-19(AZD1222)疫苗是全球最常用的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗之一;然而,很少有临床研究调查其在透析患者中的免疫原性。我们前瞻性地招募了台湾一家医疗中心的123例维持性血液透析患者。所有患者均未感染过新冠病毒,接种了两剂AZD1222疫苗,并接受了7个月的监测。主要结局是每剂疫苗接种前后以及第二剂疫苗接种后5个月的抗SARS-CoV-2受体结合域(RBD)抗体浓度,以及针对原始SARS-CoV-2、德尔塔和奥密克戎变异株的中和能力。接种疫苗后,抗SARS-CoV-2 RBD抗体滴度随时间显著升高,在第二剂疫苗接种后1个月达到峰值(中位滴度,498.8 U/mL;四分位间距,162.5至1050 U/mL),在5个月时下降了4.7倍。在第二剂疫苗接种后1个月,通过商业替代中和试验检测,分别有84.6%、83.7%和1.6%的参与者具有针对原始病毒、德尔塔变异株和奥密克戎变异株的中和抗体。针对原始病毒、德尔塔变异株和奥密克戎变异株的几何平均50%假病毒中和滴度分别为639.1、264.2和24.7。抗RBD抗体滴度与针对原始病毒和德尔塔变异株的中和能力密切相关。转铁蛋白饱和度和C反应蛋白与针对原始病毒和德尔塔变异株的中和作用相关。尽管两剂AZD1222疫苗最初在血液透析患者中引发了高抗RBD抗体滴度以及针对原始病毒和德尔塔变异株的中和作用,但很少检测到针对奥密克戎变异株的中和抗体,并且抗RBD和中和抗体随时间逐渐减弱。该人群有必要进行额外/加强接种。与普通人群相比,肾衰竭患者接种疫苗后的免疫反应较差,但很少有临床研究调查ChAdOx1 nCoV-19(AZD1222)疫苗在血液透析患者中的免疫原性。在此,我们表明两剂AZD1222疫苗导致抗SARS-CoV-2受体结合域(RBD)抗体的血清转化率很高,并且超过80%的患者获得了针对原始病毒和德尔塔变异株的中和抗体。然而,他们很少获得针对奥密克戎变异株的中和抗体。针对原始病毒的几何平均50%假病毒中和滴度比对奥密克戎变异株的高25.9倍。此外,抗RBD滴度随时间大幅下降。我们的研究结果提供了证据,支持在当前新冠疫情期间,这些患者需要采取更多保护措施,包括额外/加强接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b756/10100369/d3888e011615/spectrum.03445-22-f001.jpg

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