AbMole：QS-21的作用机理及免疫应用

AbMole：QS-21的作用机理及免疫应用在疫苗开发领域，佐剂扮演着至关重要的角色，它们能够显著增强疫苗的免疫效力。而QS-21（QA21V1，M10611，AbMole）（/products/qs-21.html）作为一种极具潜力的疫苗佐剂，在多种疫苗的研发中扮演着重要的角色。AbMole为全球科研客户提供高纯度、高生物活性的抑制剂、细胞因子、人源单抗、天然产物、荧光染料、多肽、靶点蛋白、化合物库、抗生素等试剂，全球大量文献专利引用（/）。QS-21的来源、结构和作用机理QS-21（皂苷QA21V1，M10611，AbMole）（/products/qs-21.html）是一种从智利皂皮树（Quillajasaponaria）树皮中提取的皂苷类化合物。其分子结构由四个不同的结构域组成：一个亲脂性的三萜核心、C3位置含有支链三糖，在C28位置连接了一个线性的四糖链和一个含有阿拉伯呋喃糖的二聚体酰基链（图1）ADDINEN.CITEADDINEN.CITE.DATA[1]。图1.QS-21的结构和生物合成机制ADDINEN.CITEADDINEN.CITE.DATA[1]QS-21（M10611，AbMole）（/products/qs-21.html）作为一种免疫刺激型皂苷，能够通过多种途径增强机体的免疫反应。它主要通过作用于抗原呈递细胞（如树突状细胞）和T细胞，同时刺激Th2介导的体液免疫和Th1细胞介导的免疫反应。其具体机制如下：经细胞内吞作用后，外源蛋白抗原和QS-21被递送到树突状细胞（DC）。QS-21可以介导胞内体膜的破坏，随后裂解的蛋白质抗原可以通过蛋白酶体机制在胞质溶胶中进一步加工成更小的肽片段。降解的肽通过转运蛋白易位到内质网（ER）中，并与新合成的MHCI类（MHC-I）分子结合，从而通过高尔基体囊泡迁移到DC细胞的表面，最后通过T细胞受体（TCR）将抗原肽呈递给未成熟的T淋巴细胞。2014年，AbMole的两款抑制剂分别被西班牙国家心血管研究中心和美国哥伦比亚大学用于动物体内实验，相关科研成果发表于顶刊Nature和NatureMedicine（/abmole-products-use-citations.html）。此外，QS-21（M10611，AbMole）（/products/qs-21.html）还能够激活NLRP3炎性小体，进而释放caspase-1依赖性细胞因子IL-1β和IL-18，这些细胞因子可以促进Th17细胞的成熟或驱动INF-γ介导的Th1反应ADDINEN.CITEADDINEN.CITE.DATA[2-4]。研究表明，QS-21可以促进小鼠的高抗原特异性抗体反应和CD8+T细胞反应，并有利于IgG1和IgG2a的平衡ADDINEN.CITE<EndNote><Cite><Author>Pifferi</Author><Year>2021</Year><RecNum>75</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>75</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1745906643">75</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Pifferi,C.</author><author>Fuentes,R.</author><author>Fernández-Tejada,A.</author></authors></contributors><auth-address>ChemicalImmunologyLab,CICbioGUNE,BasqueResearchandTechnologyAlliance(BRTA),Derio,BiscaySpain.GRID:grid.420175.5.ISNI:0000000406392420 Ikerbasque,BasqueFoundationforScience,Bilbao,BiscaySpain.GRID:grid.424810.b.ISNI:0000000404672314</auth-address><titles><title>Naturalandsyntheticcarbohydrate-basedvaccineadjuvantsandtheirmechanismsofaction</title><secondary-title>NatRevChem</secondary-title><alt-title>Naturereviews.Chemistry</alt-title></titles><periodical><full-title>NatRevChem</full-title><abbr-1>Naturereviews.Chemistry</abbr-1></periodical><alt-periodical><full-title>NatRevChem</full-title><abbr-1>Naturereviews.Chemistry</abbr-1></alt-periodical><pages>197-216</pages><volume>5</volume><number>3</number><edition>2021/02/02</edition><keywords><keyword>Adjuvants</keyword><keyword>Carbohydratechemistry</keyword><keyword>Carbohydrates</keyword><keyword>Chemicalmodification</keyword><keyword>Mechanismofaction</keyword><keyword>includesyntheticQS-21variantsmentionedinthiswork.C.P.andR.F.declareno</keyword><keyword>competinginterests.</keyword></keywords><dates><year>2021</year></dates><isbn>2397-3358(Print) 2397-3358</isbn><accession-num>33521324</accession-num><urls></urls><custom2>PMC7829660</custom2><electronic-resource-num>10.1038/s41570-020-00244-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。图2.QS-21相关皂苷佐剂作用机制的示意图ADDINEN.CITE<EndNote><Cite><Author>Pifferi</Author><Year>2021</Year><RecNum>75</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>75</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1745906643">75</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Pifferi,C.</author><author>Fuentes,R.</author><author>Fernández-Tejada,A.</author></authors></contributors><auth-address>ChemicalImmunologyLab,CICbioGUNE,BasqueResearchandTechnologyAlliance(BRTA),Derio,BiscaySpain.GRID:grid.420175.5.ISNI:0000000406392420 Ikerbasque,BasqueFoundationforScience,Bilbao,BiscaySpain.GRID:grid.424810.b.ISNI:0000000404672314</auth-address><titles><title>Naturalandsyntheticcarbohydrate-basedvaccineadjuvantsandtheirmechanismsofaction</title><secondary-title>NatRevChem</secondary-title><alt-title>Naturereviews.Chemistry</alt-title></titles><periodical><full-title>NatRevChem</full-title><abbr-1>Naturereviews.Chemistry</abbr-1></periodical><alt-periodical><full-title>NatRevChem</full-title><abbr-1>Naturereviews.Chemistry</abbr-1></alt-periodical><pages>197-216</pages><volume>5</volume><number>3</number><edition>2021/02/02</edition><keywords><keyword>Adjuvants</keyword><keyword>Carbohydratechemistry</keyword><keyword>Carbohydrates</keyword><keyword>Chemicalmodification</keyword><keyword>Mechanismofaction</keyword><keyword>includesyntheticQS-21variantsmentionedinthiswork.C.P.andR.F.declareno</keyword><keyword>competinginterests.</keyword></keywords><dates><year>2021</year></dates><isbn>2397-3358(Print) 2397-3358</isbn><accession-num>33521324</accession-num><urls></urls><custom2>PMC7829660</custom2><electronic-resource-num>10.1038/s41570-020-00244-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。QS-21的应用由于其强大的免疫刺激作用，QS-21（M10611，AbMole）（/products/qs-21.html）已被广泛应用于研究增强多种疫苗的效果。在肿瘤研究领域中，QS-21在实验中作为多种癌症疫苗的佐剂被使用，实验结果表明可增强肿瘤相关抗原特异性免疫反应。例如，通过与TA-MUC1（肿瘤异常糖化相关粘蛋白-1）和辅助性T细胞表位等肿瘤抗原共价结合，QS-21引发的识别癌细胞的IgG抗体反应是对照组的3倍以上ADDINEN.CITEADDINEN.CITE.DATA[5]。此外，QS-21还被用于多种黑色素瘤的抑制，例如，GM2-KLH疫苗联合QS-21在黑色素瘤小鼠模型中诱导了高水平的IgM和IgG抗体反应。图3.QS-21可提高小鼠血清中抗MUC1抗体（IgG）的水平ADDINEN.CITEADDINEN.CITE.DATA[5]QS-21（皂苷QA21V1，M10611，AbMole）（/products/qs-21.html）也在其它疫苗的研发中具有重要的应用，可用作疟疾、带状疱疹、流感等疫苗的佐剂并用于动物实验的研究。例如QS-21和单磷酸脂质A的联合能够显著增强疟疾疫苗的免疫原性。也有研究表明QS-21可以作为免疫佐剂在小鼠模型中诱导百日咳疫苗的体液和细胞反应ADDINEN.CITE<EndNote><Cite><Author>Yang</Author><Year>2023</Year><RecNum>74</RecNum><DisplayText><styleface="superscript">[6]</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1745906409">74</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yang,B.</author><author>Zhu,D.</author><author>Zhou,Y.</author><author>Gong,B.</author><author>Hu,Y.</author><author>Zhang,J.</author><author>Huang,S.</author><author>Nian,X.</author><author>Li,X.</author><author>Li,X.</author><author>Duan,K.</author><author>Yang,X.</author></authors></contributors><auth-address>NationalEngineeringTechnologyResearchCenterforCombinedVaccines,Wuhan430207,China. WuhanInstituteofBiologicalProductsCo.,Ltd.,Wuhan430207,China. NationalBiotecGroupCompanyLimited,Beijing100024,China.</auth-address><titles><title>LiposomeandQS-21CombinedAdjuvantInducestheHumoralandCellularResponsesofAcellularPertussisVaccineinaMiceModel</title><secondary-title>Vaccines(Basel)</secondary-title><alt-title>Vaccines</alt-title></titles><periodical><full-title>Vaccines(Basel)</full-title><abbr-1>Vaccines</abbr-1></periodical><alt-periodical><full-title>Vaccines(Basel)</full-title><abbr-1>Vaccines</abbr-1></alt-periodical><volume>11</volume><number>5</number><edition>2023/05/27</edition><keywords><keyword>Bordetellapertussis</keyword><keyword>adjuvant</keyword><keyword>mousemodel</keyword><keyword>tissue-residentmemoryTcell</keyword><keyword>vaccine</keyword></keywords><dates><year>2023</year><pub-dates><date>Apr28</date></pub-dates></dates><isbn>2076-393X(Print) 2076-393x</isbn><accession-num>37243018</accession-num><urls></urls><custom2>PMC10223510</custom2><electronic-resource-num>10.3390/vaccines11050914</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[6]。图4.QS-21作为百日咳疫苗的佐剂诱导小鼠的细胞免疫反应ADDINEN.CITE<EndNote><Cite><Author>Yang</Author><Year>2023</Year><RecNum>74</RecNum><DisplayText><styleface="superscript">[6]</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1745906409">74</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yang,B.</author><author>Zhu,D.</author><author>Zhou,Y.</author><author>Gong,B.</author><author>Hu,Y.</author><author>Zhang,J.</author><author>Huang,S.</author><author>Nian,X.</author><author>Li,X.</author><author>Li,X.</author><author>Duan,K.</author><author>Yang,X.</author></authors></contributors><auth-address>NationalEngineeringTechnologyResearchCenterforCombinedVaccines,Wuhan430207,China. WuhanInstituteofBiologicalProductsCo.,Ltd.,Wuhan430207,China. NationalBiotecGroupCompanyLimited,Beijing100024,China.</auth-address><titles><title>LiposomeandQS-21CombinedAdjuvantInducestheHumoralandCellularResponsesofAcellularPertussisVaccineinaMiceModel</title><secondary-title>Vaccines(Basel)</secondary-title><alt-title>Vaccines</alt-title></titles><periodical><full-title>Vaccines(Basel)</full-title><abbr-1>Vaccines</abbr-1></periodical><alt-periodical><full-title>Vaccines(Basel)</full-title><abbr-1>Vaccines</abbr-1></alt-periodical><volume>11</volume><number>5</number><edition>2023/05/27</edition><keywords><keyword>Bordetellapertussis</keyword><keyword>adjuvant</keyword><keyword>mousemodel</keyword><keyword>tissue-residentmemoryTcell</keyword><keyword>vaccine</keyword></keywords><dates><year>2023</year><pub-dates><date>Apr28</date></pub-dates></dates><isbn>2076-393X(Print) 2076-393x</isbn><accession-num>37243018</accession-num><urls></urls><custom2>PMC10223510</custom2><electronic-resource-num>10.3390/vaccines11050914</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[6]。AbMole是ChemBridge中国区官方指定合作伙伴（/chembridge-screening-libraries.html）。参考文献ADDINEN.REFLIST[1] LIUP,ZHOUJY,CHANGJH,etal.Soluplus-MediatedDiosgeninAmorphousSolidDisp