PROVENT 预防试验中突破性的 SARS-CoV-2 感染与 AZD7442（替沙格韦单抗/西加韦单抗）耐药变异株无关。
Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants.
机构信息
Vaccines and Immune Therapies, BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, Maryland, USA.
Vaccines and Immune Therapies, BioPharmaceuticals Research and Development, AstraZeneca, Cambridge, United Kingdom.
出版信息
J Infect Dis. 2023 Oct 18;228(8):1055-1059. doi: 10.1093/infdis/jiad210.
BACKGROUND
We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.
METHODS
Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.
RESULTS
At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases. SARS-CoV-2 neutralizing antibody titers were similar in breakthrough and nonbreakthrough cases.
CONCLUSIONS
Symptomatic COVID-19 breakthrough cases in PROVENT were not due to resistance-associated substitutions in AZD7442 binding sites or lack of AZD7442 exposure.
CLINICAL TRIALS REGISTRATION
NCT04625725.
背景
我们报告了从 PROVENT 暴露前预防试验突破性感染中鉴定出的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变体的基于刺突蛋白的谱系和 AZD7442（替沙吉韦单抗/西加韦单抗）中和活性。
方法
从 PROVENT 参与者中鉴定出的出现逆转录聚合酶链反应阳性症状性疾病的变体进行表型评估，以确定针对变体特异性假型病毒样颗粒的中和敏感性。
结果
在完成 6 个月的随访时，在突破性 2019 冠状病毒病（COVID-19）病例中未观察到 AZD7442 耐药变体。突破性和非突破性病例中的 SARS-CoV-2 中和抗体滴度相似。
结论
PROVENT 中的有症状 COVID-19 突破性病例不是由于 AZD7442 结合部位的耐药相关取代或缺乏 AZD7442 暴露所致。
临床试验注册
NCT04625725。
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