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尼姆斯韦单抗给药后中和呼吸道合胞病毒抗体的持久性及对婴儿呼吸道合胞病毒感染自然免疫应答的激发。

Durability of neutralizing RSV antibodies following nirsevimab administration and elicitation of the natural immune response to RSV infection in infants.

机构信息

Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Madrid, Spain.

出版信息

Nat Med. 2023 May;29(5):1172-1179. doi: 10.1038/s41591-023-02316-5. Epub 2023 Apr 24.

Abstract

Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of the respiratory syncytial virus (RSV) F protein, which has been studied in preterm and full-term infants in the phase 2b and phase 3 MELODY trials. We analyzed serum samples collected from 2,143 infants during these studies to characterize baseline levels of RSV-specific immunoglobulin G antibodies and neutralizing antibodies (NAbs), duration of RSV NAb levels following nirsevimab administration, the risk of RSV exposure during the first year of life and the infant's adaptive immune response to RSV following nirsevimab administration. Baseline RSV antibody levels varied widely; consistent with reports that maternal antibodies are transferred late in the third trimester, preterm infants had lower baseline RSV antibody levels than full-term infants. Nirsevimab recipients had RSV NAb levels >140-fold higher than baseline at day 31 and remained >50-fold higher at day 151 and >7-fold higher at day 361. Similar seroresponse rates to the postfusion form of RSV F protein in nirsevimab recipients (68-69%) compared with placebo recipients (63-70%; not statistically significant) suggest that while nirsevimab protects from RSV disease, it still allows an active immune response. In summary, nirsevimab provided sustained, high levels of NAb throughout an infant's first RSV season and prevented RSV disease while allowing the development of an immune response to RSV.

摘要

尼赛利珠单抗是一种针对呼吸道合胞病毒(RSV)F 蛋白预融合构象的延长半衰期单克隆抗体,已在 2b 期和 3 期 MELODY 试验中对早产儿和足月儿进行了研究。我们分析了这些研究中 2143 名婴儿的血清样本,以描述 RSV 特异性免疫球蛋白 G 抗体和中和抗体(NAb)的基线水平、尼赛利珠单抗给药后 RSV NAb 水平的持续时间、婴儿在生命的第一年中 RSV 暴露的风险以及尼赛利珠单抗给药后婴儿对 RSV 的适应性免疫反应。RSV 抗体基线水平差异很大;与报告称母体抗体在妊娠晚期晚期转移一致,早产儿的 RSV 抗体基线水平低于足月儿。尼赛利珠单抗受者在第 31 天的 RSV NAb 水平比基线水平高 140 多倍,在第 151 天仍保持 50 多倍,在第 361 天仍保持 7 多倍。尼赛利珠单抗受者(68-69%)与安慰剂受者(63-70%;无统计学意义)对 RSV F 蛋白融合后形式的血清反应率相似,这表明尼赛利珠单抗既能预防 RSV 疾病,又能允许产生主动免疫反应。总之,尼赛利珠单抗在婴儿的第一个 RSV 季节提供了持续的高水平 NAb,预防了 RSV 疾病,同时允许对 RSV 产生免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ab2/10202809/35ded6384f80/41591_2023_2316_Fig1_HTML.jpg

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