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基于弹性蛋白样重组体纳米系统的裂谷热病毒 DNA 疫苗传递平台。

A DNA Vaccine Delivery Platform Based on Elastin-Like Recombinamer Nanosystems for Rift Valley Fever Virus.

机构信息

BIOFORGE (Group for Advanced Materials and Nanobiotechnology), CIBER-BBN, University of Valladolid, Paseo de Belén 19, 47011, Valladolid, Spain.

Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Centro de Investigación en Sanidad Animal (CISA), Valdeolmos, 28130 Madrid, Spain.

出版信息

Mol Pharm. 2020 May 4;17(5):1608-1620. doi: 10.1021/acs.molpharmaceut.0c00054. Epub 2020 Apr 10.

Abstract

This work analyzes the immunogenicity of six genetically engineered constructs based on elastin-like recombinamers (ELRs) fused to the Gn glycoprotein from Rift Valley fever virus (RVFV). Upon transfection, all constructs showed no effect on cell viability. While fusion constructs including ELR blocks containing hydrophobic amino acids (alanine or isoleucine) did not increase the expression of viral Gn in eukaryotic cells, glutamic acid- or valine-rich fusion proteins showed enhanced expression levels compared with the constructs encoding the viral antigen alone. However, DNA plasmid immunization assays determined that the more hydrophobic constructs reduced viremia levels after RVFV challenge to a higher extent than glutamic- or valine-rich encoding plasmids and were better inducers of cellular immunity as judged by restimulation experiments. Although the Gn-ELR fusion constructs did not surpass the protective efficacy of a plasmid vaccine expressing nonfused Gn, our results warrant further experiments directed to take advantage of the immunomodulatory potential of ELR biomaterials for improving vaccines against infectious diseases.

摘要

本研究分析了六种基于弹性蛋白样重组体(ELRs)与裂谷热病毒(RVFV) Gn 糖蛋白融合的基因工程构建体的免疫原性。转染后,所有构建体对细胞活力均无影响。虽然包含疏水性氨基酸(丙氨酸或异亮氨酸)的 ELR 嵌段融合构建体并未增加真核细胞中病毒 Gn 的表达,但与单独编码病毒抗原的构建体相比,富含谷氨酸或缬氨酸的融合蛋白表现出更高的表达水平。然而,DNA 质粒免疫接种测定表明,疏水性更高的构建体在 RVFV 攻毒后降低病毒血症水平的程度高于富含谷氨酸或缬氨酸的编码质粒,并且通过再刺激实验判断,它们是更好的细胞免疫诱导剂。尽管 Gn-ELR 融合构建体并未超过表达非融合 Gn 的质粒疫苗的保护效力,但我们的结果证明有必要进一步进行实验,以利用 ELR 生物材料的免疫调节潜力来改进针对传染病的疫苗。

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