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基于壳聚糖纳米颗粒的鼻内疫苗对副球孢子菌病的生物分布及佐剂效应

Biodistribution and Adjuvant Effect of an Intranasal Vaccine Based on Chitosan Nanoparticles against Paracoccidioidomycosis.

作者信息

Santos Júnior Samuel Rodrigues Dos, Barbalho Filipe Vieira, Nosanchuk Joshua D, Amaral Andre Correa, Taborda Carlos Pelleschi

机构信息

Laboratory of Pathogenic Dimorphic Fungi, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, Brazil.

Department of Medicine and Department of Microbiology and Immunology-The Bronx, Albert Einstein College of Medicine, New York, NY 10461, USA.

出版信息

J Fungi (Basel). 2023 Feb 12;9(2):245. doi: 10.3390/jof9020245.

Abstract

Paracoccidioidomycosis (PCM) is a fungal infection caused by the thermodimorphic sp. PCM mainly affects the lungs, but, if it is not contained by the immune response, the disease can spread systemically. An immune response derived predominantly from Th1 and Th17 T cell subsets facilitates the elimination of cells. In the present work, we evaluated the biodistribution of a prototype vaccine based on the immunodominant and protective P10 peptide within chitosan nanoparticles in BALB/c mice infected with strain 18 (Pb18). The generated fluorescent (FITC or Cy5.5) or non-fluorescent chitosan nanoparticles ranged in diameter from 230 to 350 nm, and both displayed a Z potential of +20 mV. Most chitosan nanoparticles were found in the upper airway, with smaller amounts localized in the trachea and lungs. The nanoparticles complexed or associated with the P10 peptide were able to reduce the fungal load, and the use of the chitosan nanoparticles reduced the necessary number of doses to achieve fungal reduction. Both vaccines were able to induce a Th1 and Th17 immune response. These data demonstrates that the chitosan P10 nanoparticles are an excellent candidate vaccine for the treatment of PCM.

摘要

副球孢子菌病(PCM)是一种由双相真菌引起的真菌感染。PCM主要影响肺部,但如果免疫反应无法控制病情,疾病会全身扩散。主要由Th1和Th17 T细胞亚群产生的免疫反应有助于清除细胞。在本研究中,我们评估了一种基于免疫显性和保护性P10肽的原型疫苗在壳聚糖纳米颗粒中的生物分布,该疫苗用于感染18型菌株(Pb18)的BALB/c小鼠。所制备的荧光(FITC或Cy5.5)或非荧光壳聚糖纳米颗粒直径在230至350nm之间,两者的Z电位均为+20mV。大部分壳聚糖纳米颗粒存在于上呼吸道,少量分布于气管和肺部。与P10肽复合或结合的纳米颗粒能够降低真菌载量,并且使用壳聚糖纳米颗粒减少了实现真菌减少所需的剂量数。两种疫苗均能够诱导Th1和Th17免疫反应。这些数据表明,壳聚糖P10纳米颗粒是治疗PCM的优秀候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17bf/9964167/e3f28b14651b/jof-09-00245-g001.jpg

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