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黏膜给予融合前 F、糖蛋白和基质蛋白基病毒样颗粒呼吸道合胞病毒疫苗可诱导保护免疫,攻毒研究证明了这一点。

Mucosal delivery of a prefusogenic-F, glycoprotein, and matrix proteins-based virus-like particle respiratory syncytial virus vaccine induces protective immunity as evidenced by challenge studies in mice.

机构信息

Department of Communicable Diseases, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India.

Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

出版信息

Virology. 2024 Oct;598:110194. doi: 10.1016/j.virol.2024.110194. Epub 2024 Jul 31.

Abstract

RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.

摘要

呼吸道合胞病毒(RSV)感染仍然是全世界儿童的严重威胁,特别是在中低收入国家。通过黏膜途径输送疫苗具有在呼吸道中诱导局部免疫反应的巨大潜力。此前,我们基于构象稳定的预融合-F 蛋白(preFg)、糖蛋白和基质蛋白,开发了具有高度免疫原性的 RSV 病毒样颗粒(RSV-VLPs)。在这里,为了探索 RSV-VLPs 通过黏膜途径输送是否是诱导 RSV 特异性黏膜和全身免疫的有效策略,我们通过鼻腔、舌下和肺部途径将 RSV-VLPs 施用于 BALB/c 小鼠。结果表明,通过黏膜途径用 VLPs 免疫接种可引起最小的黏膜反应,但促进了适度水平的血清 IgG 抗体、增强了 T 细胞反应以及脾细胞上肺归巢标记物 CXCR3 的表达。通过所有三种黏膜途径用 VLPs 免疫接种可提供针对 RSV 攻击的保护,而没有 RSV 诱导的病理迹象。

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