Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Infect Dis. 2020 Feb 3;221(4):636-646. doi: 10.1093/infdis/jiz608.
Respiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplant (HCT) recipients. However, antibody responses that correlate with recovery from RSV disease are not fully understood.
In this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A-infected HCT recipients who recovered early (<14 days of RSV shedding) were compared with late-recovered patients (≥14 days of shedding) using gene fragment phage display libraries and surface plasmon resonance.
Anti-F serum responses were similar between these 2 groups for antibody repertoires, neutralization titers, anti-F binding antibodies (prefusion and postfusion proteins), antibody avidity, and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV G antibody repertoires in the 2 groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain. Most importantly, a significantly higher antibody affinity to RSV G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT recipients.
These findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.
呼吸道合胞病毒（RSV）感染会导致造血细胞移植（HCT）受者出现严重的发病率。然而，与 RSV 疾病恢复相关的抗体反应尚未完全了解。
在这项研究中，我们比较了急性 RSV-A 感染并早期（<14 天 RSV 脱落）恢复的 HCT 受者与晚期恢复（≥14 天脱落）患者配对的血清和鼻冲洗样本中的抗体库，使用基因片段噬菌体展示文库和表面等离子体共振技术。
对于抗体库、中和滴度、抗 F 结合抗体（融合前和融合后蛋白）、抗体亲合力和与特定抗原表位的结合，这两组的抗 F 血清反应相似。相比之下，早期恢复患者的鼻冲洗液对包含 p27 的 F 肽的结合更高。虽然两组血清 RSV G 抗体库相似，但早期恢复和晚期恢复患者之间最强的差异是鼻冲洗抗体的滴度，尤其是对中央保守域的结合。最重要的是，与晚期恢复的 HCT 受者相比，早期恢复患者的鼻冲洗液中对 RSV G 的抗体亲和力明显更高。
这些发现强调了黏膜抗体在解决上呼吸道 RSV-A 感染中的重要性。
