陆军军医大学学报2026，Vol.48Issue(8)：991-1002,12.DOI:10.16016/j.2097-0927.202512118
脂质纳米颗粒作为重组蛋白疫苗佐剂通过增强Th1/Th17应答保护幽门螺杆菌感染
Lipid nanoparticles as adjuvants for recombinant protein vaccine protect against Helicobacter pylori infection by enhancing Th1/Th17 responses
摘要
Abstract
Objective Helicobacter pylori(Hp)infection is prevalent worldwide and represents a risk factor for various chronic inflammatory and neoplastic gastric diseases.In recent years,lipid nanoparticles(LNPs)have demonstrated broad application prospects in vaccine adjuvant research owing to their favorable delivery capacity and immunomodulatory potential.Preparation of LNPs and evaluation of their immunoenhancing effects as adjuvants for a Helicobacter pylori recombinant protein vaccine,as well as their protective efficacy against H.pylori infection.Methods LNPs were prepared using microfluidic technology,with morphology examined by transmission electron microscopy and particle size and polydispersity index characterized by dynamic light scattering.The activating effects of LNPs on bone marrow-derived dendritic cells(BMDCs)were evaluated in vitro.For in vivo experiments,female BALB/c mice(6 to 8 weeks old,weighing 17 to 20 g)were randomly divided into(n=10):PBS group,UreB/NapA group,and LNP-H+UreB/NapA group.Mice were immunized by intramuscular injection on days 0,14,and 28.Serum specific antibody titers were measured by ELISA at day 14 after the final immunization,and IFN-γ and IL-17A secretion in mouse spleens was detected by ELISpot.Mice were challenged with H.pylori to establish an infection model.At 4 weeks post-infection,H.pylori colonization in gastric tissue was quantified by probe-based real-time PCR,and adhesion inhibition ability of immunized mice against H.pylori was evaluated through in vitro AGS cell adhesion assay.Results The prepared LNPs exhibited uniform morphology,with mean particle size of 100 to 120 nm and polydispersity index of 0.1 to 0.2.LNPs promoted the phagocytosis of antigens by BMDCs and significantly increase the expression levels of costimulatory molecules CD80,CD86,and CD40 on BMDC surfaces(P<0.001),indicating potential to promote BMDC maturation.LNPs also significantly enhanced the secretions of IL-6 and IL-1β in the supernatants of BMDCs(P<0.0001).When combined with UreB and NapA,LNPs remarkably elevated the serum titers of specific total IgG,IgG1,and IgG2a(P<0.05),and promoted the secretions of specific IFN-γ and IL-17A by splenic lymphocytes(P<0.05),suggesting that LNPs strengthen specific T-cell immune responses.Furthermore,LNPs reduced the colonization of H.pylori in mouse gastric tissues and significantly inhibited the adhesion to gastric mucosal epithelial cells.Conclusion LNPs can serve as an effective adjuvant for H.pylori recombinant protein vaccines,effectively enhancing humoral and cellular immune responses and conferring protective effects against H.pylori infection.关键词
幽门螺杆菌/疫苗佐剂/脂质纳米颗粒Key words
Helicobacter pylori/vaccine adjuvant/lipid nanoparticle分类
医药卫生引用本文复制引用
朱吉,王亚兰,邓炎,余文康,江悦,张苗苗,李海波..脂质纳米颗粒作为重组蛋白疫苗佐剂通过增强Th1/Th17应答保护幽门螺杆菌感染[J].陆军军医大学学报,2026,48(8):991-1002,12.基金项目
国家自然科学基金面上项目(32270988) （32270988）
重庆市自然科学基金面上项目(CSTB2024NSCQ-MSX0981) Supported by the General Program of National Natural Science Foundation of China(32270988)and the General Project of Natural Science Foundation of Chongqing(CSTB2024NSCQ-MSX0981). （CSTB2024NSCQ-MSX0981）
