机构:[1]Shenzhen Univ, Med Sch, Inst Inheritance Based Innovat Chinese Med, Sch Pharm,Guangdong Prov Key Lab Chinese Med Ingre, Shenzhen 518055, Peoples R China[2]Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Dept Pharm, Kunming 650034, Yunnan, Peoples R China[3]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China中山大学附属第二医院[4]Nanjing Tech Univ, Res Inst Biomat, Tech Inst Adv Mat, Coll Mat Sci & Engn,Bioinspired Biomed Mat & Devic, Nanjing 211816, Peoples R China
Conventional aluminum adjuvants exhibit limited cellular immunity. Polyinosinic-polycytidylic acid (poly I:C) activates cytoplasmic retinoic acid-inducible gene-like receptor (RLR), triggering strong T cell activation and cellular responses. However, when applied as an adjuvant, its limited endocytosis and restricted cytoplasmic delivery diminish its effectiveness and increase its toxicity. Hybrid polymer-lipid nanoparticle (PLNP) possesses numerous benefits such as good stability, reduced drug leakage, simple fabrication, easy property modulation, and excellent reproducibility compared to the lipid nanoparticle or the polymeric vector. Here, we developed a novel cationic polymer-lipid hybrid adjuvant capable of incorporating poly I:C to enhance cellular immunity. The hepatitis B surface antigen (HBsAg) was immobilized onto poly I:C-incorprated PLNP (PPLNP) via electrostatic interactions, forming the HBsAg/PPLNP vaccine formulation. The PPLNP adjuvant largely enhanced the cellular endocytosis and cytoplasmic transport of poly I:C, activating RLR followed by promoting type I interferon (IFN) secretion. Meanwhile, PPLNP obviously enhanced the antigen uptake, prolonged antigen retention at the site of administration, and facilitated enhanced transport of antigens to lymph nodes. The HBsAg/PPLNP nanovaccine led to amplified concentrations of antigen-specific immunoglobulin G (IgG), IFN-gamma, granzyme B, and an enhanced IgG2a/IgG1 ratio, alongside the FasL+/CD8+ T cell activation, favoring a T helper 1 (TH1)-driven immune response. PPLNP, distinguished by its biocompatibility, ease of fabrication, and effectiveness in augmenting cellular immunity, holds significant promise as a new adjuvant.
基金:
Guang Dong Basic and Applied Basic Research Foundation [2023A1515110428]; Shenzhen High-level Talent Scientific Research Start-up Foundation [827-000743]; Shenzhen Medical Research Fund [D2401001]; National Natural Science Foundation of China [82003276, 32101068]; Jiangsu Distinguished Professor Program, Research Project of the First People's Hospital of Yunnan Province [KHBS-2020-011]; Research Project of the Clinical Pharmacy Center of Yunnan Province [2023YJZX-YX05]
第一作者机构:[1]Shenzhen Univ, Med Sch, Inst Inheritance Based Innovat Chinese Med, Sch Pharm,Guangdong Prov Key Lab Chinese Med Ingre, Shenzhen 518055, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Liu Xuhan,Min Qiuxia,Li Yihui,et al.Enhanced Cellular Immunity for Hepatitis B Virus Vaccine: A Novel Polyinosinic-Polycytidylic Acid-Incorporated Adjuvant Leveraging Cytoplasmic Retinoic Acid-Inducible Gene-Like Receptor Activation and Increased Antigen Uptake[J].BIOMATERIALS RESEARCH.2024,28:doi:10.34133/bmr.0096.
APA:
Liu, Xuhan,Min, Qiuxia,Li, Yihui&Chen, Siyuan.(2024).Enhanced Cellular Immunity for Hepatitis B Virus Vaccine: A Novel Polyinosinic-Polycytidylic Acid-Incorporated Adjuvant Leveraging Cytoplasmic Retinoic Acid-Inducible Gene-Like Receptor Activation and Increased Antigen Uptake.BIOMATERIALS RESEARCH,28,
MLA:
Liu, Xuhan,et al."Enhanced Cellular Immunity for Hepatitis B Virus Vaccine: A Novel Polyinosinic-Polycytidylic Acid-Incorporated Adjuvant Leveraging Cytoplasmic Retinoic Acid-Inducible Gene-Like Receptor Activation and Increased Antigen Uptake".BIOMATERIALS RESEARCH 28.(2024)