A broadly applicable protein-polymer adjuvant system for antiviral vaccines.

IF 9 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EMBO Molecular Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI:10.1038/s44321-024-00076-4
Caiqian Wang, Yuanyuan Geng, Haoran Wang, Zeheng Ren, Qingxiu Hou, An Fang, Qiong Wu, Liqin Wu, Xiujuan Shi, Ming Zhou, Zhen F Fu, Jonathan F Lovell, Honglin Jin, Ling Zhao
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Abstract

Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.

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广泛适用于抗病毒疫苗的蛋白质聚合物佐剂系统。
尽管蛋白亚单位疫苗通常具有可接受的安全性和精确的抗原含量,但有限的免疫原性会导致体液免疫和细胞免疫效果不理想,因此需要疫苗佐剂和递送系统。在此,我们评估了一种疫苗佐剂系统,该系统由藜芦皂-21(QS-21)和卟啉钴聚合物胶束组成,可在其表面显示 His 标记的抗原。这种纳米级胶束能促进抗原吸收和树突状细胞活化,从而诱导强大的细胞毒性 T 淋巴细胞反应和生殖中心的形成。利用甲型流感和狂犬病病毒的重组蛋白抗原,胶束佐剂系统激发了强大的抗病毒反应,保护小鼠免受致命挑战。此外,该系统还可与其他抗原结合,在三种高致病性病毒病原体模型中诱导高滴度的中和抗体:埃博拉病毒、马尔堡病毒和尼帕病毒。总之,我们的研究结果表明,这种聚合物胶束佐剂系统可用作开发抗病毒疫苗对策的有效纳米平台,促进体液免疫和细胞免疫。
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来源期刊
EMBO Molecular Medicine
EMBO Molecular Medicine 医学-医学:研究与实验
CiteScore
17.70
自引率
0.90%
发文量
105
审稿时长
4-8 weeks
期刊介绍: EMBO Molecular Medicine is an open access journal in the field of experimental medicine, dedicated to science at the interface between clinical research and basic life sciences. In addition to human data, we welcome original studies performed in cells and/or animals provided they demonstrate human disease relevance. To enhance and better specify our commitment to precision medicine, we have expanded the scope of EMM and call for contributions in the following fields: Environmental health and medicine, in particular studies in the field of environmental medicine in its functional and mechanistic aspects (exposome studies, toxicology, biomarkers, modeling, and intervention). Clinical studies and case reports - Human clinical studies providing decisive clues how to control a given disease (epidemiological, pathophysiological, therapeutic, and vaccine studies). Case reports supporting hypothesis-driven research on the disease. Biomedical technologies - Studies that present innovative materials, tools, devices, and technologies with direct translational potential and applicability (imaging technologies, drug delivery systems, tissue engineering, and AI)
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