Assessment of neutralizing antibody response as a correlate of protection against symptomatic SARS-CoV-2 infections after administration of two doses of the CoronaVac inactivated COVID-19 vaccine: A phase III randomized controlled trial

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2024-10-16 DOI:10.1016/j.jinf.2024.106315

Xinhua Chen , Xing Meng , Qianhui Wu , Wey Wen Lim , Qianqian Xin , Benjamin J. Cowling , Weining Meng , Hongjie Yu , Dimas Tadeu Covasa

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引用次数: 0

Abstract

Background

The emergence of variants of concerns of SARS-CoV-2 highlights the need for comprehensively elucidating the correlates of protection for different COVID-19 vaccine types. Inactivated COVID-19 vaccines are currently amongst the most widely administered vaccines globally. However, investigations into the correlates of protection for inactivated COVID-19 vaccines are relatively rare.

Methods

Data from a phase III double-blind, randomized, placebo-controlled clinical trial (NCT0445659) that evaluated the efficacy and safety of the CoronaVac vaccine in healthcare professionals were utilized in this secondary analysis. Additionally, the correlation between neutralizing antibody levels measured by micro-cytopathic effect (CPE) neutralization assay and the occurrence of laboratory-confirmed infections was assessed using neutralizing antibodies measured in blood samples collected on day 28 after receiving two doses of the vaccine. Finally, the protective threshold required to provide 50% protection against symptomatic illness and virus infections was estimated.

Results

The risk of infection was negatively correlated with the levels of post-vaccination neutralizing antibodies measured on day 28 after the second dose. A neutralization titer of 30 (95% CI: 2–56) was predicted to provide 50% efficacy against symptomatic infection, whilst a titer of 42 (95% CI: 24–62) was predicted to provide 50% efficacy against total infection. Lastly, a neutralization titer of 247 (95% CI: 139–506) or higher was required to achieve 80% or higher protection against symptomatic infections.

Conclusions

The results highlight the value of neutralizing antibody response as a correlate of protection, which can be used to inform future vaccine development and implementation. Further studies of immune correlates of protection for other vaccines are warranted.

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评估中和抗体反应作为接种两剂 CoronaVac COVID-19 灭活疫苗后对无症状 SARS-CoV-2 感染的保护作用的相关因素：III期随机对照试验。

背景：令人担忧的 SARS-CoV-2 变异株的出现凸显了全面阐明不同 COVID-19 疫苗类型的保护相关性的必要性。COVID-19 灭活疫苗是目前全球接种最广泛的疫苗之一。然而，对 COVID-19 灭活疫苗保护相关性的调查却相对较少：本二次分析采用了一项 III 期双盲、随机、安慰剂对照临床试验（NCT0445659）的数据，该试验评估了 CoronaVac 疫苗对医护人员的有效性和安全性。此外，还利用接种两剂疫苗后第 28 天采集的血样中测得的中和抗体，评估了微小细胞病理效应 (CPE) 中和测定法测得的中和抗体水平与实验室确诊感染发生率之间的相关性。最后，还估算了对无症状疾病和病毒感染提供 50%保护所需的保护阈值：结果：感染风险与接种第二剂疫苗后第 28 天测得的接种后中和抗体水平呈负相关。预测中和滴度为 30（95% CI：2-56）时，对无症状感染的有效率为 50%，而滴度为 42（95% CI：24-62）时，对全部感染的有效率为 50%。最后，中和滴度达到247（95% CI：139-506）或更高，才能对无症状感染产生80%或更高的保护作用：结论：研究结果凸显了中和抗体反应作为保护相关因素的价值，可为未来疫苗的开发和实施提供参考。有必要进一步研究其他疫苗的免疫保护相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.