Nanostructured Lipid Carriers Overcome the Low Immunogenicity of M2e Peptide via Surface Click Chemistry Conjugation, Improving the Anti-M2e Antibody Response

IF 4.8 Q2 ENGINEERING, BIOMEDICAL
Advanced Nanobiomed Research Pub Date : 2026-04-04 Epub Date: 2026-02-15 DOI:10.1002/anbr.202500236
Louis Bourlon, Carole Fournier, Antoine Hoang, Christine Charrat, Alban Lepetitcolin, Jessica Morlieras, Fabrice Navarro, Patrice N. Marche
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引用次数: 0

Abstract

Influenza vaccines targeting hemagglutinin require annual updates due to viral variability, limiting protection against pandemic strains. The conserved matrix protein 2 ectodomain (M2e) peptide offers cross-strain immunity but suffers from low immunogenicity. Here, M2e peptides are conjugated onto nanostructured lipid carriers (NLCs) using bioorthogonal click chemistry, preserving key epitopes and enhancing antigen presentation. Immunization in mice demonstrates that NLC-M2e induces focused and robust anti-M2e antibody responses, which are significantly amplified by incorporating a pan-DR epitope helper T cell epitope, achieving antibody levels compatible with protection. The formulation elicits balanced IgG subclasses and T-helper 1 cell-type cellular responses, supporting effective immune mechanisms. These findings suggest that NLC-based delivery of M2e peptides, especially with helper epitopes, represents a promising universal influenza vaccine strategy warranting further preclinical and clinical investigation.

Abstract Image

纳米结构脂质载体通过表面点击化学偶联克服M2e肽的低免疫原性,提高抗M2e抗体应答
由于病毒变异,针对血凝素的流感疫苗需要每年更新,限制了对大流行毒株的保护。保守的基质蛋白2外结构域(M2e)肽提供跨株免疫,但免疫原性低。在这里,M2e肽被结合到纳米结构脂质载体(NLCs)上,使用生物正交点击化学,保存关键表位并增强抗原呈递。小鼠免疫实验表明,NLC-M2e诱导了集中和强大的抗m2e抗体反应,通过加入泛dr表位辅助T细胞表位,这种抗体反应被显著放大,达到与保护相容的抗体水平。该制剂引起平衡的IgG亚类和t -辅助性1细胞型细胞反应,支持有效的免疫机制。这些发现表明,基于nlc的M2e肽递送,特别是辅助表位,代表了一种有希望的通用流感疫苗策略,值得进一步的临床前和临床研究。
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来源期刊
Advanced Nanobiomed Research
Advanced Nanobiomed Research nanomedicine, bioengineering and biomaterials-
CiteScore
5.00
自引率
5.90%
发文量
87
审稿时长
21 weeks
期刊介绍: Advanced NanoBiomed Research will provide an Open Access home for cutting-edge nanomedicine, bioengineering and biomaterials research aimed at improving human health. The journal will capture a broad spectrum of research from increasingly multi- and interdisciplinary fields of the traditional areas of biomedicine, bioengineering and health-related materials science as well as precision and personalized medicine, drug delivery, and artificial intelligence-driven health science. The scope of Advanced NanoBiomed Research will cover the following key subject areas: ▪ Nanomedicine and nanotechnology, with applications in drug and gene delivery, diagnostics, theranostics, photothermal and photodynamic therapy and multimodal imaging. ▪ Biomaterials, including hydrogels, 2D materials, biopolymers, composites, biodegradable materials, biohybrids and biomimetics (such as artificial cells, exosomes and extracellular vesicles), as well as all organic and inorganic materials for biomedical applications. ▪ Biointerfaces, such as anti-microbial surfaces and coatings, as well as interfaces for cellular engineering, immunoengineering and 3D cell culture. ▪ Biofabrication including (bio)inks and technologies, towards generation of functional tissues and organs. ▪ Tissue engineering and regenerative medicine, including scaffolds and scaffold-free approaches, for bone, ligament, muscle, skin, neural, cardiac tissue engineering and tissue vascularization. ▪ Devices for healthcare applications, disease modelling and treatment, such as diagnostics, lab-on-a-chip, organs-on-a-chip, bioMEMS, bioelectronics, wearables, actuators, soft robotics, and intelligent drug delivery systems. with a strong focus on applications of these fields, from bench-to-bedside, for treatment of all diseases and disorders, such as infectious, autoimmune, cardiovascular and metabolic diseases, neurological disorders and cancer; including pharmacology and toxicology studies.
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