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替沙格韦单抗联合西加韦单抗(AZD7442)对不同严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体的中和能力评估:一项与接种疫苗人群对比的病例报告研究

Evaluation of Neutralizing Capacity of Tixagevimab plus Cilgavimab (AZD7442) against Different SARS-CoV-2 Variants: A Case Report Study with Comparison to a Vaccinated Population.

作者信息

Gillot Constant, Bayart Jean-Louis, Maloteau Vincent, Dogné Jean-Michel, Douxfils Jonathan, Favresse Julien

机构信息

Clinical Pharmacology and Toxicology Research Unit Namur Research Institute for Life Sciences University of Namur, Namur 5000, Belgium.

Department of Laboratory Medicine Clinique St-Pierre, Ottignies, Belgium.

出版信息

Case Rep Infect Dis. 2024 Aug 31;2024:9163490. doi: 10.1155/2024/9163490. eCollection 2024.

Abstract

AZD7442 (150 mg of tixagevimab plus 150 mg of cilgavimab) has been approved for the preexposure prophylaxis of COVID-19 and for the treatment of adults and adolescents with COVID-19 who do not require supplemental oxygen and who are at increased risk of severe COVID-19. Thus, the aim of the present study is to evaluate the neutralizing capacity of tixagevimab and cilgavimab across different SARS-CoV-2 variants in two patients who received AZD7442 for immunoprophylaxis. A cohort of subjects ( = 45) who had received the BNT162b2 mRNA COVID-19 vaccine has been included to compare these two preventive strategies. Neutralizing antibody (NAb) titers against several variants were assessed against the wild-type, alpha, beta, gamma, delta, omicron BA.5, and XBB.1.5 variants. Binding antibodies have also been measured. NAbs for AZD7442 was 8.1 days (95% CI: 5.1-19.5 days) and was 11.8 days (95% CI: 7.9-23.7 days) for the primo-vaccination cohort. The time to reach neutralization negativity was 108.3 days (95% CI: 66.9-130.7) for AZD7442 compared to 95.4 days (95% CI: 31.0-119.7 days) for the primo-vaccination cohort. The time to reach NAbs' negativity differs between variants with the maximum value obtained for alpha (i.e., 101.1 days (95% CI: 30.0-135.4 days)) and the minimum obtained for beta (i.e., 61.2 days (95% CI: 37.8-77.1 days)). Our results reinforce the need of reviewing the use of AZD7442 in relation to variants of concern and potentially adapting its administration schedule. AZD7442 could be indicated for short-term prophylaxis in frail patients who may be acutely exposed to SARS-CoV-2.

摘要

AZD7442(替沙格韦单抗150毫克加西加韦单抗150毫克)已被批准用于新冠病毒暴露前预防,以及治疗不需要补充氧气且有重症新冠病毒感染高风险的成年和青少年新冠病毒感染者。因此,本研究的目的是评估在两名接受AZD7442进行免疫预防的患者中,替沙格韦单抗和西加韦单抗对不同严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变异株的中和能力。纳入了一组接受BNT162b2 mRNA新冠疫苗的受试者(n = 45)以比较这两种预防策略。评估了针对野生型、阿尔法、贝塔、伽马、德尔塔、奥密克戎BA.5和XBB.1.5变异株的中和抗体(NAb)滴度。还检测了结合抗体。AZD7442组达到中和抗体的时间为8.1天(95%置信区间:5.1 - 19.5天),初次接种疫苗队列的时间为11.8天(95%置信区间:7.9 - 23.7天)。与初次接种疫苗队列的95.4天(9%置信区间:31.0 - 119.7天)相比,AZD7442组达到中和抗体阴性的时间为108.3天(95%置信区间:66.9 - 130.7天)。达到中和抗体阴性的时间在不同变异株之间有所不同,阿尔法变异株最长(即101.1天(95%置信区间:30.0 - 135.4天)),贝塔变异株最短(即61.2天(95%置信区间:37.8 - 77.1天))。我们的结果强化了根据关注变异株情况审查AZD7442使用并可能调整其给药方案的必要性。AZD7442可用于可能急性暴露于SARS-CoV-2的体弱患者的短期预防。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0a2/11380708/04459f7c6048/CRIID2024-9163490.001.jpg

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