关键词: Delivery routes Mucosal vaccine Nasal Pulmonary Respiratory syncytial virus (RSV) Sublingual Virus-like-particles (VLPs)

Mesh : Animals Respiratory Syncytial Virus Infections / prevention & control immunology Respiratory Syncytial Virus Vaccines / immunology administration & dosage Mice, Inbred BALB C Mice Antibodies, Viral / blood immunology Vaccines, Virus-Like Particle / immunology administration & dosage Viral Fusion Proteins / immunology genetics administration & dosage Female Viral Matrix Proteins / immunology administration & dosage genetics Immunity, Mucosal Immunoglobulin G / blood immunology Respiratory Syncytial Virus, Human / immunology Lung / virology immunology Glycoproteins / immunology administration & dosage Administration, Mucosal Respiratory Syncytial Viruses / immunology T-Lymphocytes / immunology

来  源:   DOI:10.1016/j.virol.2024.110194

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:
RSV感染仍然是全世界儿童的严重威胁,尤其是,在中低收入国家。经由粘膜的疫苗递送具有在呼吸道中诱导局部免疫应答的巨大潜力。以前,我们报道了高免疫原性RSV病毒样颗粒(RSV-VLP)的发展,其基础是构象稳定的前-F蛋白(preFg),糖蛋白和基质蛋白。这里,探讨RSV-VLPs的粘膜递送是否是诱导RSV特异性粘膜和全身免疫的有效策略,RSV-VLP经鼻给药,BALB/c小鼠的舌下和肺部途径。结果表明,通过粘膜途径用VLP免疫诱导最小的粘膜反应,但促进适度水平的血清IgG抗体,增强的T细胞反应和脾细胞上肺归巢标志物CXCR3的表达。通过所有三种粘膜途径用VLP免疫提供针对RSV攻击的保护,而没有RSV诱导的病理学的迹象。
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