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经鼻腔免疫接种呼吸道合胞病毒亚单位疫苗诱导黏膜免疫和保护作用。

Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation.

机构信息

VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.

Veterinary Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.

出版信息

J Gen Virol. 2014 Feb;95(Pt 2):301-306. doi: 10.1099/vir.0.058461-0. Epub 2013 Oct 17.

Abstract

The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (ΔF) protein formulated with polyI : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8(+) T-cells in the lung, when delivered intranasally. Furthermore, this ΔF protein formulation promoted the production of CD8(+) central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of ΔF protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The ΔF protein formulation was confirmed to be highly efficacious and safe in cotton rats.

摘要

大多数感染,包括由呼吸道合胞病毒(RSV)引起的感染,发生在黏膜表面。由于目前尚无 RSV 疫苗,我们的目标是生产一种有效的亚单位疫苗,并使用适合黏膜传递和交叉呈递的佐剂。用多聚肌苷酸:胞苷酸(一种先天防御调节剂肽和聚磷腈)配制的 RSV 融合(ΔF)蛋白的截断分泌版本,通过鼻腔内给药,可诱导局部和全身免疫,包括 RSV F 特异性 IgG、IgA 和病毒中和抗体的亲和力成熟,以及在肺部的 F 特异性 CD8(+)T 细胞。此外,这种ΔF 蛋白配方可促进纵隔淋巴结中 CD8(+)中央记忆 T 细胞的产生,并提供 RSV 攻击的保护。用这种佐剂组合配制的ΔF 蛋白可增强肺树突状细胞的摄取和向引流淋巴结的转运。在棉鼠中,该ΔF 蛋白配方被证实具有高效和安全性。

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