Peptide-TLR7/8a-Coordinated DNA Vaccines Elicit Enhanced Immune Responses against Infectious Diseases

被引：1

作者：

Yang, Rong ^{[1
]}

Yao, Tingting ^{[1
]}

Xu, Jinliang ^{[1
]}

Liu, Xiaoxiao ^{[1
]}

Yang, Yaqi ^{[1
]}

Ding, Junqiang ^{[2
,3
]}

Cao, Cong ^{[1
]}

Su, Runping ^{[1
]}

Li, Sha ^{[1
]}

Lu, Wuyuan ^{[1
]}

Gao, Xihui ^{[1
]}

机构：

[1] Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Sch Basic Med Sci, Key Lab Med Mol Virol MOE NHC CAMS, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Pudong Hosp, Sch Pharm, Shanghai 201203, Peoples R China

[3] Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Shanghai 201203, Peoples R China

来源：

ACS BIOMATERIALS SCIENCE & ENGINEERING | 2024年

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

DNA vaccines; poly(beta amino esters); genedelivery; toll-like receptor 7/8 agonist; nanoparticles; POLYMERIC NANOPARTICLES; GENE; AGONISTS;

D O I：

10.1021/acsbiomaterials.4c00749

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(beta-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral zeta potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.

引用

页码：4374 / 4387

页数：14

共 49 条

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