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泊洛沙姆具有佐剂特性,可增加颗粒状抗原在远处淋巴结的传播。

Poloxamers Have Vaccine-Adjuvant Properties by Increasing Dissemination of Particulate Antigen at Distant Lymph Nodes.

机构信息

Laboratory of Tissue Biology and Therapeutic Engineering, Institut de Biologie et Chimie des Protéines, UMR 5305, CNRS/Claude Bernard University Lyon 1, 7 Passage du Vercors, CEDEX 07, 69367 Lyon, France.

Laboratory of Virology and Genetics, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

出版信息

Molecules. 2023 Jun 15;28(12):4778. doi: 10.3390/molecules28124778.

Abstract

Vaccine technology is still facing challenges regarding some infectious diseases, which can be addressed by innovative drug delivery systems. In particular, nanoparticle-based vaccines combined with new types of adjuvants are actively explored as a platform for improving the efficacy and durability of immune protection. Here, biodegradable nanoparticles carrying an antigenic model of HIV were formulated with two combinations of poloxamers, 188/407, presenting or not presenting gelling properties, respectively. The study aimed to determine the influence of poloxamers (as a thermosensitive hydrogel or a liquid solution) on the adaptive immune response in mice. The results showed that poloxamer-based formulations were physically stable and did not induce any toxicity using a mouse dendritic cell line. Then, whole-body biodistribution studies using a fluorescent formulation highlighted that the presence of poloxamers influenced positively the dissemination profile by dragging nanoparticles through the lymphatic system until the draining and distant lymph nodes. The strong induction of specific IgG and germinal centers in distant lymph nodes in presence of poloxamers suggested that such adjuvants are promising components in vaccine development.

摘要

疫苗技术在某些传染病方面仍然面临挑战,可以通过创新的药物传递系统来解决。特别是,基于纳米粒子的疫苗与新型佐剂结合,被积极探索作为提高免疫保护效果和持久性的平台。在这里,携带 HIV 抗原模型的可生物降解纳米颗粒分别与两种泊洛沙姆组合(188/407)进行了配制,分别具有或不具有凝胶特性。本研究旨在确定泊洛沙姆(作为热敏水凝胶或液体溶液)对小鼠适应性免疫反应的影响。结果表明,基于泊洛沙姆的制剂在使用小鼠树突状细胞系时物理稳定且没有诱导任何毒性。然后,使用荧光制剂进行全身生物分布研究表明,泊洛沙姆的存在通过将纳米颗粒拖过淋巴系统来积极影响其扩散谱,直到引流和远处的淋巴结。在存在泊洛沙姆的情况下,远处淋巴结中特异性 IgG 和生发中心的强烈诱导表明,此类佐剂是疫苗开发中很有前途的成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208a/10304813/08b458112b9e/molecules-28-04778-g001.jpg

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