基于红细胞的疫苗载体研究进展*

doi:10.3969/j.issn.1671-2587.2024.03.018

临床输血与检验 ›› 2024, Vol. 26 ›› Issue (3): 404-411.DOI: 10.3969/j.issn.1671-2587.2024.03.018

基于红细胞的疫苗载体研究进展^*

甘丽¹, 易平¹, 赵勤俭², 张馨元¹

¹四川大学华西口腔医院,四川成都 610041;
²重庆医科大学药学院,重庆 400016

收稿日期:2024-02-24 出版日期:2024-06-20 发布日期:2024-06-24
通讯作者: 张馨元,主要从事微纳米颗粒免疫刺激剂的开发及其免疫机制研究,（E-mail）xinyuan_zhang925@scu.edu.cn。
作者简介:甘丽,主要从事免疫学检验方面研究,（E-mail）2667312275@qq.com。
基金资助:
*国家自然科学基金项目（No.32070925）资助

Research Progress on Erythrocyte-based Vaccine Carriers

GAN Li¹, YI Ping¹, ZHAO Qinjian², ZHANG Xinyuan¹

¹West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan;
²College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R.

Received:2024-02-24 Online:2024-06-20 Published:2024-06-24

摘要/Abstract

摘要： 红细胞在机体内含量丰富,主要功能是运输氧气。成熟哺乳动物红细胞无细胞核和细胞器,且比表面积大、易于修饰,是理想的递送载体,已被广泛用于药物递送。红细胞还具有免疫调节功能。红细胞能够结合循环中的病原体并与趋化因子相互作用参与固有免疫应答。衰老的红细胞通过调节膜表面分子的表达,与脾脏中的吞噬细胞相互作用,从而调节适应性免疫应答,使衰老红细胞最终以非炎症途径被清除。基于红细胞在递送和免疫调节方面的优势,红细胞载体开始用于新型疫苗中传统疫苗佐剂的替代。基于红细胞载体的合成方法多样,生物安全性良好且易于修饰,能够满足不同疫苗的需求。处于不同阶段的红细胞载体通过设计能够发挥不同的免疫调节功能。基于正常红细胞的载体能够诱导免疫激活,而基于衰老红细胞的载体可用于诱导免疫耐受,在肿瘤、传染病、自身免疫性疾病的预防和治疗中均有良好效果。本文从红细胞作为疫苗载体的生物学优势、基于红细胞的疫苗载体与抗原的作用形式及其免疫效果、红细胞载体的优化策略等方面进行综述,为新型疫苗的研发提供方向。

关键词: 疫苗, 红细胞, 递送载体, 免疫激活, 免疫耐受

Abstract: Erythrocytes are abundant within the body and are predominantly responsible for oxygen delivery. Mature mammalian erythrocytes have no nucleus and organelles, and they possess a high surface area-to-volume ratio, making them easy to conduct modification. These characteristics make erythrocytes suitable as delivery system, and erythrocytes have been used for drug delivery. Erythrocytes also possess immune regulatory capabilities. Erythrocytes can bind to pathogens and interact with chemokines, participating in innate immunity. Senescent erythrocytes modulate the expression of surface molecules and interact with phagocytic cells in the spleen, thereby regulating the adaptive immune response, facilitating the clearance of senescent erythrocytes through non-inflammatory pathways. The advantages in delivery and immunomodulation have led to the use of erythrocyte-based carriers in novel vaccines, replacing traditional vaccine adjuvants. There are diverse methods for synthesis of erythrocyte-based carriers. These carriers have great biocompatibility and are amenable to modification, accommodating the needs of different vaccines. By design, carriers based on erythrocytes in different stages can exert different immunomodulatory functions. Carriers based on normal erythrocytes can induce immune activation, while those based on senescent erythrocytes can be used to induce immune tolerance, showing promising results in the prevention and treatment of cancer, infectious diseases and autoimmune diseases. This article reviews the biological advantages of erythrocyte as vaccine carriers, antigen-loading strategies, the immunological effects of erythrocyte-based vaccine carriers and optimization strategies, providing insights for the development of novel vaccines.

Key words: Vaccine, Erythrocyte, Carrier, Immune activation, Immune tolerance

中图分类号:

R331.1⁺41

甘丽, 易平, 赵勤俭, 张馨元. 基于红细胞的疫苗载体研究进展^*[J]. 临床输血与检验, 2024, 26(3): 404-411.

GAN Li, YI Ping, ZHAO Qinjian, ZHANG Xinyuan. Research Progress on Erythrocyte-based Vaccine Carriers[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(3): 404-411.

参考文献

[1] WANG F,ZONG R L,CHEN G.Erythrocyte-enabled immunomodulation for vaccine delivery[J].J Control Release,2022,341:314-328.
[2] ZHANG X Y,ZHANG Z G,XIA N S,et al.Carbohydrate-containing nanoparticles as vaccine adjuvants[J].Expert Rev Vaccines,2021,20(7):797-810.
[3] ZHAO T M,CAI Y L,JIANG Y J,et al.Vaccine adjuvants:mechanisms and platforms[J].Signal Transduct Target Ther,2023,8(1):283.
[4] LUO Z Q,SUN L Y,BIAN F K,et al.Erythrocyte-inspired functional materials for biomedical applications[J].Adv Sci (Weinh),2023,10(6):e2206150.
[5] VILLA C H,CINES D B,SIEGEL D L,et al.Erythrocytes as carriers for drug delivery in blood transfusion and beyond[J].Transfus Med Rev,2017,31(1):26-35.
[6] YAO H Z,WANG Z G,WANG N,et al.Enhancing circulation and tumor accumulation of carboplatin via an erythrocyte-anchored prodrug strategy[J].Angew Chem Int Ed Engl,2022,61(25):e202203838.
[7] IZZATI MAT RANI N N,ALZUBAIDI Z M,AZHARI H,et al.Novel engineering:Biomimicking erythrocyte as a revolutionary platform for drugs and vaccines delivery[J].Eur J Pharmacol,2021,900:174009.
[8] 韩冰,汤思淇,朱大帷,等.新型疫苗佐剂研究进展[J].中国畜牧兽医,2023,50(6):2460-2467.
[9] LIN Y H,WANG X,HUANG X F,et al.Calcium phosphate nanoparticles as a new generation vaccine adjuvant[J].Expert Rev Vaccines,2017,16(9):895-906.
[10] 张鹏,毛彤瑶,段招军.腺病毒载体疫苗的研究进展[J].中国人兽共患病学报,2023,39(7):695-703.
[11] ANDERSON H L,BRODSKY I E,MANGALMURTI N S.The evolving erythrocyte:red blood cells as modulators of innate immunity[J].J Immunol,2018,201(5):1343-1351.
[12] MINASYAN H.Phagocytosis and oxycytosis:two arms of human innate immunity[J].Immunol Res,2018,66(2):271-280.
[13] MINASYAN H.Erythrocyte:bacteria killer and bacteria pray[J].Int J Immunol,2015,3(1):1.
[14] MORERA D,MACKENZIE S A.Is there a direct role for erythrocytes in the immune response?[J].Vet Res,2011,42(1):89.
[15] SHEN H,SCHUSTER R,STRINGER K F,et al.The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth[J].FASEB J,2006,20(1):59-64.
[16] ARIAS C F,ARIAS C F.How do red blood cells know when to die?[J].R Soc Open Sci,2017,4(4):160850.
[17] OLDENBORG P A,ZHELEZNYAK A,FANG Y F,et al.Role of CD47 as a marker of self on red blood cells[J].Science,2000,288(5473):2051-2054.
[18] BARCLAY A N,VAN DEN BERG T K.The interaction between signal regulatory protein alpha (SIRPα) and CD47:structure,function,and therapeutic target[J].Annu Rev Immunol,2014,32:25-50.
[19] FERGUSON T A,CHOI J,GREEN D R.Armed response:how dying cells influence T-cell functions[J].Immunol Rev,2011,241(1):77-88.
[20] KONTOS S,KOURTIS I C,DANE K Y,et al.Engineering antigens for in situ erythrocyte binding induces T-cell deletion[J].Proc Natl Acad Sci U S A,2013,110(1): E60-E68.
[21] YI T S,LI J H,CHEN H,et al.Splenic dendritic cells survey red blood cells for missing self-CD47 to trigger adaptive immune responses[J].Immunity,2015,43(4):764-775.
[22] SHI W,QIU Q Q,FENG Z Y,et al.Design,synthesis and immunological evaluation of self-assembled antigenic peptides from dual-antigen targets:a broad-spectrum candidate for an effective antibreast cancer therapy[J].J Immunother Cancer,2021,9(6):e002523.
[23] LI S,CHEN D Z,GUO H Q,et al.IMM47,a humanized monoclonal antibody that targets CD24,exhibits exceptional anti-tumor efficacy by blocking the CD24/Siglec-10 interaction and can be used as monotherapy or in combination with anti-PD1 antibodies for cancer immunotherapy[J].Antib Ther,2023,6(4):240-252.
[24] LI D,XIONG W,WANG Y D,et al.SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors[J].Sci Immunol,2022,7(67):eabj5501.
[25] CANNY S P,OROZCO S L,THULIN N K,et al.Immune mechanisms in inflammatory Anemia[J].Annu Rev Immunol,2023,41:405-429.
[26] MCCRACKEN M N,CHA A C,WEISSMAN I L.Molecular pathways:activating T cells after cancer cell phagocytosis from blockade of CD47 “don’t eat me” signals[J].Clin Cancer Res,2015,21(16):3597-3601.
[27] KHALAJI A,YANCHESHMEH F B,FARHAM F,et al.Don’t eat me/eat me signals as a novel strategy in cancer immunotherapy[J].Heliyon,2023,9(10):e20507.
[28] 彭培培,胡娇.红细胞伪装纳米颗粒:一个具有潜力的药物及疫苗递送系统[J].生物工程学报,2023,39(1):159-176.
[29] ANSELMO A C,GUPTA V,ZERN B J,et al.Delivering nanoparticles to lungs while avoiding liver and spleen through adsorption on red blood cells[J].ACS Nano,2013,7(12):11129-11137.
[30] UKIDVE A,ZHAO Z M,FEHNEL A,et al.Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function[J].Proc Natl Acad Sci USA,2020,117(30):17727-17736.
[31] SUN X Q,HAN X,XU L G,et al.Surface-engineering of red blood cells as artificial antigen presenting cells promising for cancer immunotherapy[J].Small,2017,13(40):10.1002/smll.201701864.
[32] BOBERG A,DOMINICI S,BRAVE A,et al.Immunization with HIV protease peptides linked to syngeneic erythrocytes[J].Infect Agent Cancer,2007,2:9.
[33] WANG L,WANG X Y,YANG F M,et al.Systemic antiviral immunization by virus-mimicking nanoparticles-decorated erythrocytes[J].Nano Today,2021,40:101280.
[34] GAO L P,WANG H,NAN L J,et al.Erythrocyte membrane-wrapped pH sensitive polymeric nanoparticles for non-small cell lung cancer therapy[J].Bioconjug Chem,2017,28(10):2591-2598.
[35] SU J,ZHANG R,LIAN Y M,et al.Preparation and characterization of erythrocyte membrane-camouflaged berberine hydrochloride-loaded gelatin nanoparticles[J].Pharmaceutics,2019,11(2):93.
[36] SPUGNINI E P,ARANCIA G,PORRELLO A,et al.Ultrastructural modifications of cell membranes induced by “electroporation” on melanoma xenografts[J].Microsc Res Tech,2007,70(12):1041-1050.
[37] MURRAY A M,PEARSON I F S,FAIRBANKS L D,et al.The mouse immune response to carrier erythrocyte entrapped antigens[J].Vaccine,2006,24(35/36):6129-6139.
[38] GUO Y Y,WANG D,SONG Q L,et al.Erythrocyte membrane-enveloped polymeric nanoparticles as nanovaccine for induction of antitumor immunity against melanoma[J].ACS Nano,2015,9(7):6918-6933.
[39] ZHAI Y W,HE X R,LI Y,et al.A splenic-targeted versatile antigen courier:iPSC wrapped in coalescent erythrocyte-liposome as tumor nanovaccine[J].Sci Adv,2021,7(35):eabi6326.
[40] WANG Y M,JI X,RUAN M L,et al.Worm-like biomimetic nanoerythrocyte carrying siRNA for melanoma gene therapy[J].Small,2018,14(47):e1803002.
[41] JIANG Q,LIU Y,GUO R R,et al.Erythrocyte-cancer hybrid membrane-camouflaged melanin nanoparticles for enhancing photothermal therapy efficacy in tumors[J].Biomaterials,2019,192:292-308.
[42] HAN X,SHEN S F,FAN Q,et al.Red blood cell-derived nanoerythrosome for antigen delivery with enhanced cancer immunotherapy[J].Sci Adv,2019,5(10):eaaw6870.
[43] ZHANG X Q,LUO M Y,DASTAGIR S R,et al.Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic[J].Nat Commun,2021,12(1):2637.
[44] HUANG N J,PISHESHA N,MUKHERJEE J,et al.Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin[J].Nat Commun,2017,8(1):423.
[45] PISHESHA N,BILATE A M,WIBOWO M C,et al.Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease[J].Proc Natl Acad Sci USA,2017,114(12):3157-3162.
[46] CREMEL M,GUÉRIN N,HORAND F,et al.Red blood cells as innovative antigen carrier to induce specific immune tolerance[J].Int J Pharm,2013,443(1/2):39-49.
[47] SHI J H,KUNDRAT L,PISHESHA N,et al.Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes[J].Proc Natl Acad Sci USA,2014,111(28):10131-10136.
[48] PAN D C,MYERSON J W,BRENNER J S,et al.Nanoparticle properties modulate their attachment and effect on carrier red blood cells[J].Sci Rep,2018,8(1):1615.
[49] CHAMBERS E,MITRAGOTRI S.Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes[J].J Control Release,2004,100(1):111-119.
[50] PAN D,VARGAS-MORALES O,ZERN B,et al.The effect of polymeric nanoparticles on biocompatibility of carrier red blood cells[J].PLoS One,2016,11(3):e0152074.
[51] DEHAINI D,WEI X L,FANG R H,et al.Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization[J].Adv Mater,2017,29(16):10.1002/adma.201606209.
[52] YAN J J,YU J C,WANG C,et al.Red blood cells for drug delivery[J].Small Meth,2017,1(12):1700270.
[53] DOSHI N,ZAHR A S,BHASKAR S,et al.Red blood cell-mimicking synthetic biomaterial particles[J].Proc Natl Acad Sci USA,2009,106(51):21495-21499.

基于红细胞的疫苗载体研究进展^*

Research Progress on Erythrocyte-based Vaccine Carriers

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们

[1]	红细胞血型抗原拓展匹配适用范围中国专家共识编写组. 红细胞血型抗原拓展匹配适用范围中国专家共识[J]. 临床输血与检验, 2024, 26(3): 289-298.
[2]	孟炜程, 陈要臻, 王雅芬, 安宁, 刘志新, 吴晓双, 王斐, 胡兴斌. 致敏红细胞BPGM酶活性降低对红细胞携氧/释氧能力的影响研究^*[J]. 临床输血与检验, 2024, 26(3): 308-314.
[3]	吴常睿, 黄远帅, 王洁. 吸烟对红细胞影响的相关研究进展^*[J]. 临床输血与检验, 2024, 26(3): 411-419.
[4]	中国输血协会临床输血管理学专业委员会. 术前深度单采自体红细胞和/或血小板储血技术应用中国专家共识[J]. 临床输血与检验, 2024, 26(2): 145-155.
[5]	范瑞, 封春雨, 王雨婧, 尚玮玮, 唐文飞, 马海梅, 张欢. 体外模拟加压输血对悬浮红细胞质量影响的研究^*[J]. 临床输血与检验, 2024, 26(2): 223-229.
[6]	葛晓芹, 付恒, 胡官林, 曹彩霞, 杨维涛, 王振兴, 周国琼, 付竹筠, 孙婧雯, 沈有华, 燕锋, 鲍琳, 林富文, 李丽, 王泽颖, 冯兰洁, 周竞, 康美艳, 张剑, 刘保霞, 汤文隽, 郭萍莉, 李浩, 邱艳. 新冠肺炎疫情对国内25家地级市中心血站全血制备成分血的供应影响分析^*[J]. 临床输血与检验, 2024, 26(2): 244-250.
[7]	李洋, 杨明峰, 王莹, 张坚, 刘嘉馨, 孙保亮. 血红蛋白类氧载体的研究进展及应用前景^*[J]. 临床输血与检验, 2024, 26(2): 282-288.
[8]	中国输血协会临床输血管理学专业委员会. 婴儿期输血前红细胞血型血清学检测中国专家共识^*[J]. 临床输血与检验, 2024, 26(1): 8-16.
[9]	杨晓樨, 赵营营, 马吉芳, 于政. 硅芯片纳米微流体技术与磁激活细胞分选法对胎儿有核红细胞富集效果的比较[J]. 临床输血与检验, 2024, 26(1): 86-91.
[10]	尤来委, 姚娜, 吴曼迪, 张岩, 崔应辉, 郭建荣. 不同配方保存液对2型糖尿病患者贮存式自体红细胞保护作用的对比研究^*[J]. 临床输血与检验, 2023, 25(6): 721-726.
[11]	赵兴丹, 翁艾罕. 极低出生体重儿输血及输血量的影响因素及其预测模型构建[J]. 临床输血与检验, 2023, 25(6): 758-766.
[12]	冯娜, 兰静, 曹鑫, 丁谨, 景媛媛. X射线与γ射线辐照对悬浮红细胞质量影响的对比研究[J]. 临床输血与检验, 2023, 25(5): 594-598.
[13]	陈婷婷, 赵丽坤, 卓海龙, 骆群. ABO不同血型在不同保存期内CD38的表达[J]. 临床输血与检验, 2023, 25(5): 613-618.
[14]	付晓艳, 甄自达, 邱立娟, 张慧敏, 王孟键, 马曙轩. 红细胞储存时间与体外循环心脏手术患儿术后急性肾损伤的关系[J]. 临床输血与检验, 2023, 25(4): 489-493.
[15]	张静, 王素玲, 乔芳, 赵佳, 胡光磊, 王振雷. NEC患儿T抗原暴露导致红细胞多凝集现象的鉴定及输血策略[J]. 临床输血与检验, 2023, 25(4): 494-497.