Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases

Yongmei Liu; Jianhua Lu; Haoting Zhan; Wenfang Yuan; Xiaomeng Li; Haiyan Kang; Haolong Li; Yongliang Chen; Linlin Cheng; Xingli Sun; Haojie Zheng; Wei Wang; Erhei Dai; Yongzhe Li

doi:10.1016/j.virs.2023.07.005

October 2023

Yongmei Liu, Jianhua Lu, Haoting Zhan, Wenfang Yuan, Xiaomeng Li, Haiyan Kang, Haolong Li, Yongliang Chen, Linlin Cheng, Xingli Sun, Haojie Zheng, Wei Wang, Erhei Dai and Yongzhe Li. Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases[J]. Virologica Sinica, 2023, 38(5): 723-734. doi: 10.1016/j.virs.2023.07.005

Citation: Yongmei Liu, Jianhua Lu, Haoting Zhan, Wenfang Yuan, Xiaomeng Li, Haiyan Kang, Haolong Li, Yongliang Chen, Linlin Cheng, Xingli Sun, Haojie Zheng, Wei Wang, Erhei Dai, Yongzhe Li. Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases .VIROLOGICA SINICA, 2023, 38(5) : 723-734. http://dx.doi.org/10.1016/j.virs.2023.07.005

灭活SARS-CoV-2加强剂疫苗显著增加慢性肝病患者的免疫应答

刘永梅 ^a ,
卢建华 ^c ,
詹皓婷 ^a ,
袁文芳 ^b ,
李晓萌 ^a,d ,
康海燕 ^b ,
李昊隆 ^a ,
陈勇良 ^b ,
程琳琳 ^a ,
孙杏丽 ^b ,
郑浩杰 ^b ,
王慰 ^b ,
戴二黑 ^b,, ,
李永哲 ^a,,

a 中国医学科学院北京协和医学院北京协和医院, 疑难重症及罕见病国家重点实验室, 检验科, 北京, 100730;
b 河北医科大学石家庄第五医院肝病科, 石家庄, 050021;
c 河北医科大学石家庄第五医院检验科, 石家庄, 050021;
d 北京大学人民医院检验科, 北京, 100035

通讯作者： 戴二黑, daieh2008@126.com; 李永哲, yongzhelipumch@126.com
收稿日期： 2023-04-20
录用日期： 2023-07-19

摘要

慢性肝病可增加COVID-19重症和死亡风险，然而灭活SARS-CoV-2加强剂疫苗刺激慢性肝病患者抗体反应的有效性尚不清楚。因此，我们进行了一项横断面研究，纳入了237例成年慢性肝病患者和170例年龄、疫苗接种时间匹配的健康对照，使用SARS-CoV-2替代病毒中和试验检测血清抗SARS-CoV-2野生型和BA.4/5中和抗体,分别使用间接ELISA和双抗原夹心ELISA检测抗新冠病毒S蛋白受体结合区域(Receptor binding domain，RBD) IgG、总抗SARS-CoV-2抗体。慢性肝病患者接种第三剂灭活疫苗后总抗SARS-CoV-2抗体水平、抗RBD IgG水平及野生型和BA.4/5中和抗体抑制率均较加强针前明显升高，而与健康对照相比则相对降低。加强疫苗接种后诱导的抗体反应随时间减弱。BA.4/5中和抗体抑制率在加强针后有所提高，但低于阳性抑制阈值。重症肝病（包括肝硬化和肝癌）患者四种SARS-CoV-2特异性抗体，包括总抗SARS-CoV-2抗体水平、抗RBD IgG水平及野生型和BA.4/5中和抗体抑制率，明显低于非重症肝病患者。慢性肝病患者血清SARS-CoV-2特异性抗体阳性率也低于健康对照。慢性肝病患者接受加强剂SARS-CoV-2灭活疫苗后注射后，年龄、末次接种时间是BA.4/5中和抗体阳性率的危险因素。此外，白细胞计数和乙肝病毒核心抗体作为保护性因素，重症肝病作为危险因素，与总抗SARS-CoV-2抗体血清阳性率相关。总体来说，我们的数据发现加强剂SARS-CoV-2灭活疫苗后，慢性肝病患者的抗体反应有所改善，并在接种后120天达到峰值，随后除抗SARS-CoV-2抗体外，所有抗体均下降。慢性肝病患者对疫苗的免疫反应受损，BA.4/5中和抗体较野生型中和抗体弱，阻碍了加强剂注射对奥密克戎变异株流行的保护作用。需要进一步评估细胞免疫反应，以确定慢性肝病患者加强注射的最佳数量和时间间隔。
- 慢性肝病
- , 新型冠状病毒灭活疫苗
- , 加强针
- , 抗体反应
- , 免疫反应

Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases

a. Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China;
b. Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China;
c. Department of Clinical Laboratory, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China;
d. Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100035, China

Corresponding author: Erhei Dai, daieh2008@126.com Yongzhe Li, yongzhelipumch@126.com
Received Date: 20 April 2023
Accepted Date: 19 July 2023

Abstract

Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
- Chronic liver disease (CLD)
- , SARS-CoV-2 inactivated vaccines
- , Booster vaccination
- , Antibody response
- , Immune response

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10.1016j.virs.2023.07.005-ESM.docx