A Synthetic Liposome Nanoparticle Vaccine Platform for Broad-Spectrum Vaccine Design.

IF 9.1 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2025-10-01 DOI:10.1021/acs.nanolett.5c03021

Mo Zhang, Zihan Gao, Sheng Feng, Xun Wang, Huaiyu Wang, Chumeng Yang, Xiaolei Lin, Zhiqiang Xu, Nan Zhang, Yiyang Li, Haochen Tian, Ningyi Jin, Bin Yu, Pengfei Wang, Chang Li, Xianghui Yu

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Abstract

Emerging viruses such as SARS-CoV-2 and HIV-1 pose major challenges for traditional vaccines due to their rapid mutation and immune evasion. Here, we present a modular liposomal nanoparticle (LNP) vaccine platform integrating trimeric immunogens and synergistic adjuvants to induce broad and durable immunity. Using a self-assembled SARS-CoV-2 RBD trimer (RM) based on MTQ and Ni²⁺/His-tag coupling, antigens were directionally displayed on LNPs coloaded with QS-21, MPLA, and R848 adjuvants. This RM-LNP formulation enhanced antigen stability, lymph node targeting, and germinal center responses, eliciting high titers of broadly neutralizing antibodies and strong T and memory B cell immunity. The RM-LNP vaccine conferred potent neutralization against Omicron subvariants and protected hACE2 mice from Delta, BA.5, and XBB infection. Extension to HIV-1 vaccine design also demonstrated significant and broad neutralization against Tier 2 strains. This study offers a versatile nanovaccine strategy for combating highly mutable viruses.

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用于广谱疫苗设计的合成脂质体纳米颗粒疫苗平台。

新出现的病毒，如SARS-CoV-2和HIV-1，由于其快速突变和免疫逃避，对传统疫苗构成了重大挑战。在这里，我们提出了一个模块化的脂质体纳米颗粒（LNP）疫苗平台，整合三聚体免疫原和协同佐剂，以诱导广泛和持久的免疫。利用基于MTQ和Ni2+/ his标签偶联的自组装SARS-CoV-2 RBD三聚体（RM），抗原定向显示在装载了QS-21、MPLA和R848佐剂的LNPs上。这种RM-LNP制剂增强了抗原稳定性、淋巴结靶向性和生发中心反应，引发高滴度的广泛中和抗体和强大的T和记忆B细胞免疫。RM-LNP疫苗对Omicron亚变体具有有效的中和作用，并保护hACE2小鼠免受Delta、BA.5和XBB感染。扩展到HIV-1疫苗设计也显示出对Tier 2毒株具有显著和广泛的中和作用。这项研究为对抗高度易变性病毒提供了一种通用的纳米疫苗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.