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用 Th1/Th2 平衡佐剂配制融合前 RSV F 蛋白可在 RSV 经验丰富的年轻小鼠中提供完全保护,而不会产生 Th2 偏向性免疫。

Formulation of the prefusion RSV F protein with a Th1/Th2-balanced adjuvant provides complete protection without Th2-skewed immunity in RSV-experienced young mice.

机构信息

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA; Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA; Department of Medicine, Division of Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Vaccine. 2020 Sep 22;38(41):6357-6362. doi: 10.1016/j.vaccine.2020.08.023. Epub 2020 Aug 20.

Abstract

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections among infants with most infections occurring in the first year of life. Multiple RSV exposures are required for children to mount adult-like immune responses. Although adult RSV immunity is associated with less severe disease, the protection induced through natural infection is short-lived. Therefore, vaccination of RSV-experienced young children may accelerate immunity and provide long-term protection from RSV reinfection. However, the extent to which different Th-biased vaccine regimens influence pre-existing humoral and cellular immunity in RSV-experienced young children is unknown. To address this question, infant BALB/c mice were RSV-infected and subsequently immunized with the prefusion RSV F (PreF) antigen formulated with either a Th2-skewing (Alum) or Th1/Th2-balanced (Advax-SM) adjuvant. These studies show that both adjuvants boosted neutralizing antibody and protected from RSV reinfection, but Advax-SM adjuvant prevented the Th2-skewed immunity observed in RSV-experienced young mice immunized with PreF/Alum.

摘要

呼吸道合胞病毒(RSV)是导致婴儿下呼吸道感染的主要原因,大多数感染发生在生命的第一年。儿童需要多次 RSV 暴露才能产生成人样的免疫反应。虽然成人 RSV 免疫力与疾病的严重程度较低相关,但通过自然感染诱导的保护是短暂的。因此,对 RSV 有经验的幼儿进行疫苗接种可能会加速免疫反应,并提供长期的 RSV 再感染保护。然而,不同的 Th 偏向疫苗方案在多大程度上影响 RSV 有经验的幼儿中已有的体液和细胞免疫尚不清楚。为了解决这个问题,用 RSV 感染了 RSV 经验丰富的婴儿 BALB/c 小鼠,然后用 Th2 偏向(铝佐剂)或 Th1/Th2 平衡(Advax-SM 佐剂)配制的前融合 RSV F(PreF)抗原进行免疫。这些研究表明,两种佐剂都能增强中和抗体并预防 RSV 再感染,但 Advax-SM 佐剂预防了用 PreF/Alum 免疫的 RSV 经验丰富的幼鼠中观察到的 Th2 偏向免疫。

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