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Key roles of adjuvants in modern vaccines. <i>Nat. Med.<\/i>, <b>19<\/b>, 1597\u20131608 (2013).","DOI":"10.1038\/nm.3409"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Zhao T, Cai Y, Jiang Y, He X, Wei Y, Yu Y, Tian X. Vaccine adjuvants: mechanisms and platforms. <i>Signal Transduct. Target. Ther.<\/i>, <b>8<\/b>, 283 (2023).","DOI":"10.1038\/s41392-023-01557-7"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Lee SM, Kim P, You J, Kim EH. Role of damage-associated molecular pattern\/cell death pathways in vaccine-induced immunity. <i>Viruses<\/i>, <b>13<\/b>, 2340 (2021).","DOI":"10.3390\/v13122340"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Marichal T, Ohata K, Bedoret D, Mesnil C, Sabatel C, Kobiyama K, Lekeux P, Coban C, Akira S, Ishii KJ, Bureau F, Desmet CJ. DNA released from dying host cells mediates aluminum adjuvant activity. <i>Nat. Med.<\/i>, <b>17<\/b>, 996\u20131002 (2011).","DOI":"10.1038\/nm.2403"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Li H, Willingham SB, Ting JP-Y, Re F. Cutting edge: inflammasome activation by alum and alum\u2019s adjuvant effect are mediated by NLRP3. <i>J. Immunol.<\/i>, <b>181<\/b>, 17\u201321 (2008).","DOI":"10.4049\/jimmunol.181.1.17"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Kim EH, Woodruff MC, Grigoryan L, Maier B, Lee SH, Mandal P, Cortese M, Natrajan MS, Ravindran R, Ma H, Merad M, Gitlin AD, Mocarski ES, Jacob J, Pulendran B. Squalene emulsion-based vaccine adjuvants stimulate CD8 T cell, but not antibody responses, through a RIPK3-dependent pathway. <i>eLife<\/i>, <b>9<\/b>, e52687 (2020).","DOI":"10.7554\/eLife.52687"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Alving CR, Rao M, Matyas GR. Similarities and differences of chemical compositions and physical and functional properties of adjuvant system 01 and army liposome formulation with QS21. <i>Front. Immunol.<\/i>, <b>14<\/b>, 1102524 (2023).","DOI":"10.3389\/fimmu.2023.1102524"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Zarnegar B, Carow B, Eriksson J, Spennare E, \u00d6hlund P, Akpinar E, Bringeland E, Osterman IL, Lundqvist L, Antti J, Handin N, Helgesson PH, Bankefors J, L\u00f6vgren Bengtsson K, Sellin ME, Palm AKE, Stertman L, Lunderius Andersson C. Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization. <i>NPJ Vaccines<\/i>, <b>10<\/b>, 184 (2025).","DOI":"10.1038\/s41541-025-01243-5"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Rajput ZI, Hu SH, Xiao CW, Arijo AG. Adjuvant effects of saponins on animal immune responses. <i>J. Zhejiang Univ. Sci. B<\/i>, <b>8<\/b>, 153\u2013161 (2007).","DOI":"10.1631\/jzus.2007.B0153"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Marciani DJ. Elucidating the mechanisms of action of saponin-derived adjuvants. <i>Trends Pharmacol. Sci.<\/i>, <b>39<\/b>, 573\u2013585 (2018).","DOI":"10.1016\/j.tips.2018.03.005"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Wang P. Natural and synthetic saponins as vaccine adjuvants. <i>Vaccines<\/i>, <b>9<\/b>, 222 (2021).","DOI":"10.3390\/vaccines9030222"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Marty-Roix R, Vladimer GI, Pouliot K, Weng D, Buglione-Corbett R, West K, MacMicking JD, Chee JD, Wang S, Lu S, Lien E. Identification of QS-21 as an inflammasome-activating molecular component of saponin adjuvants. <i>J. Biol. Chem.<\/i>, <b>291<\/b>, 1123\u20131136 (2016).","DOI":"10.1074\/jbc.M115.683011"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Wilson NS, Duewell P, Yang B, Li Y, Marsters S, Koernig S, Latz E, Maraskovsky E, Morelli AB, Schnurr M, Ashkenazi A. Inflammasome-dependent and -independent IL-18 production mediates immunity to the ISCOMATRIX adjuvant. <i>J. Immunol.<\/i>, <b>192<\/b>, 3259\u20133268 (2014).","DOI":"10.4049\/jimmunol.1302011"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Blevins HM, Xu Y, Biby S, Zhang S. The NLRP3 inflammasome pathway: a review of mechanisms and inhibitors for the treatment of inflammatory diseases. <i>Front. Aging Neurosci.<\/i>, <b>14<\/b>, 879021 (2022).","DOI":"10.3389\/fnagi.2022.879021"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Ramos S, Hartenian E, Broz P. Programmed cell death: NINJ1 and mechanisms of plasma membrane rupture. <i>Trends Biochem. Sci.<\/i>, <b>49<\/b>, 717\u2013728 (2024).","DOI":"10.1016\/j.tibs.2024.05.007"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Kayagaki N, Kornfeld OS, Lee BL, <i>et al<\/i>. NINJ1 mediates plasma membrane rupture during lytic cell death. <i>Nature<\/i>, <b>591<\/b>, 131\u2013136 (2021).","DOI":"10.1038\/s41586-021-03218-7"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Ramos S, Hartenian E, Santos JC, Walch P, Broz P. NINJ1 induces plasma membrane rupture and release of damage-associated molecular pattern molecules during ferroptosis. <i>EMBO J.<\/i>, <b>43<\/b>, 1164\u20131186 (2024).","DOI":"10.1038\/s44318-024-00055-y"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Dondelinger Y, Priem D, Huyghe J, Delanghe T, Vandenabeele P, Bertrand MJM. NINJ1 is activated by cell swelling to regulate plasma membrane permeabilization during regulated necrosis. <i>Cell Death Dis.<\/i>, <b>14<\/b>, 755 (2023).","DOI":"10.1038\/s41419-023-06284-z"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Zhu L, Xu Y. Multifaceted roles of ninjurin1 in immunity, cell death, and disease. <i>Front. Immunol.<\/i>, <b>16<\/b>, 1519519 (2025).","DOI":"10.3389\/fimmu.2025.1519519"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) David L, Borges JP, Hollingsworth LR, Volchuk A, Jansen I, Garlick E, Steinberg BE, Wu H. NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. <i>Cell<\/i>, <b>187<\/b>, 2224\u20132235.e16 (2024).","DOI":"10.1016\/j.cell.2024.03.008"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Kovarova M, Hesker PR, Jania L, Nguyen M, Snouwaert JN, Xiang Z, Lommatzsch SE, Huang MT, Ting JP-Y, Koller BH. NLRP1-dependent pyroptosis leads to acute lung injury and morbidity in mice. <i>J. Immunol.<\/i>, <b>189<\/b>, 2006\u20132016 (2012).","DOI":"10.4049\/jimmunol.1201065"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Kamstrup S, San Martin R, Doberti A, Grande H, Dalsgaard K. Preparation and characterisation of quillaja saponin with less heterogeneity than Quil-A. <i>Vaccine<\/i>, <b>18<\/b>, 2244\u20132249 (2000).","DOI":"10.1016\/S0264-410X(99)00560-5"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Wu CA, Yang YW. Induction of cell death by saponin and antigen delivery. <i>Pharm. Res.<\/i>, <b>21<\/b>, 271\u2013277 (2004).","DOI":"10.1023\/B:PHAM.0000016239.04067.66"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Borges JP, S\u00e6tra RSR, Volchuk A, Bugge M, Devant P, Sporsheim B, Kilburn BR, Evavold CL, Kagan JC, Goldenberg NM, Flo TH, Steinberg BE. Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. <i>eLife<\/i>, <b>11<\/b>, e78609 (2022).","DOI":"10.7554\/eLife.78609"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Kayagaki N, Stowe IB, Alegre K, <i>et al<\/i>. Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury. <i>Nature<\/i>, <b>618<\/b>, 1072\u20131077 (2023).","DOI":"10.1038\/s41586-023-06191-5"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Zahid A, Li B, Kombe AJK, Jin T, Tao J. Pharmacological inhibitors of the NLRP3 inflammasome. <i>Front. Immunol.<\/i>, <b>10<\/b>, 2538 (2019).","DOI":"10.3389\/fimmu.2019.02538"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Schachter J, Guijarro A, Angosto-Bazarra D, Pinilla M, Hurtado-Navarro L, Meunier E, P\u00e9rez-Oliva AB, Schwarzbaum PJ, Pelegrin P. Gasdermin D mediates a fast transient release of ATP after NLRP3 inflammasome activation before ninjurin 1-induced lytic cell death. <i>Cell Rep.<\/i>, <b>44<\/b>, 115233 (2025).","DOI":"10.1016\/j.celrep.2025.115233"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Ahn BJ, Le H, Shin MW, Bae SJ, Lee EJ, Wee HJ, Cha JH, Lee HJ, Lee HS, Kim JH, Kim CY, Seo JH, Lo EH, Jeon S, Lee MN, Oh GT, Yin GN, Ryu JK, Suh JK, Kim KW. Ninjurin1 deficiency attenuates susceptibility of experimental autoimmune encephalomyelitis in mice. <i>J. Biol. Chem.<\/i>, <b>289<\/b>, 3328\u20133338 (2014).","DOI":"10.1074\/jbc.M113.498212"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Ramos-Junior ES, Morandini AC. Gasdermin: a new player to the inflammasome game. <i>Biomed. J.<\/i>, <b>40<\/b>, 313\u2013316 (2017).","DOI":"10.1016\/j.bj.2017.10.002"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Degen M, Santos JC, Pluhackova K, Cebrero G, Ramos S, Jankevicius G, Hartenian E, Guillerm U, Mari SA, Kohl B, M\u00fcller DJ, Schanda P, Maier T, Perez C, Sieben C, Broz P, Hiller S. Structural basis of NINJ1-mediated plasma membrane rupture in cell death. <i>Nature<\/i>, <b>618<\/b>, 1065\u20131071 (2023).","DOI":"10.1038\/s41586-023-05991-z"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Kwak MS, Kim HS, Lee B, Kim YH, Son M, Shin JS. Immunological significance of HMGB1 post-translational modification and redox biology. <i>Front. Immunol.<\/i>, <b>11<\/b>, 1189 (2020).","DOI":"10.3389\/fimmu.2020.01189"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. <i>Annu. Rev. Immunol.<\/i>, <b>29<\/b>, 139\u2013162 (2011).","DOI":"10.1146\/annurev-immunol-030409-101323"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Chen GY, Tang J, Zheng P, Liu Y. CD24 and siglec-10 selectively repress tissue damage-induced immune responses. <i>Science<\/i>, <b>323<\/b>, 1722\u20131725 (2009).","DOI":"10.1126\/science.1168988"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Detienne S, Welsby I, Collignon C, Wouters S, Coccia M, Delhaye S, Van Maele L, Thomas S, Swertvaegher M, Detavernier A, Elouahabi A, Goriely S, Didierlaurent AM. Central role of CD169<sup>+<\/sup> lymph node resident macrophages in the adjuvanticity of the QS-21 component of AS01. <i>Sci. 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