{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:34:05Z","timestamp":1792190045697,"version":"4.4.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UKRI|MRC|Medical Research Council","award":["MC_UU_00008\/1"],"award-info":[{"award-number":["MC_UU_00008\/1"]}]},{"name":"UKRI|MRC|Medical Research Council","award":["MR\/K012037"],"award-info":[{"award-number":["MR\/K012037"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["100954"],"award-info":[{"award-number":["100954"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015691","name":"HHS|NIH|NIAID|Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI00645"],"award-info":[{"award-number":["AI00645"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"HHS|NIH|NIAID|Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI144371"],"award-info":[{"award-number":["AI144371"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"UKRI|Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M011224\/1"],"award-info":[{"award-number":["BB\/M011224\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Rep"],"published-print":{"date-parts":[[2021,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination.<\/jats:p>","DOI":"10.15252\/embr.202152447","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T03:27:48Z","timestamp":1623986868000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2671-4488","authenticated-orcid":false,"given":"Lise","family":"Chauveau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bridgeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiong K","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Beveridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe N","family":"Frost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Rijal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela","family":"Pedroza-Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Partridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Gilbert-Jaramillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-9780","authenticated-orcid":false,"given":"Persephone","family":"Borrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hal","family":"Drakesmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain R","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-835X","authenticated-orcid":false,"given":"Jan","family":"Rehwinkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"BFEMBR202152447_CR1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature12306","volume":"498","author":"A Ablasser","year":"2013","unstructured":"Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Rohl I, Hopfner KP, Ludwig J, Hornung V (2013) cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature 498: 380\u2013384","journal-title":"Nature"},{"key":"BFEMBR202152447_CR2","doi-asserted-by":"crossref","first-page":"492","DOI":"10.4049\/jimmunol.1301812","volume":"192","author":"SM Blaauboer","year":"2014","unstructured":"Blaauboer SM, Gabrielle VD, Jin L (2014) MPYS\/STING-mediated TNF-alpha, not type I IFN, is essential for the mucosal adjuvant activity of (3'-5')-cyclic-di-guanosine-monophosphate in\u00a0vivo. J Immunol 192: 492\u2013502","journal-title":"J Immunol"},{"key":"BFEMBR202152447_CR3","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.06670","volume":"4","author":"SM Blaauboer","year":"2015","unstructured":"Blaauboer SM, Mansouri S, Tucker HR, Wang HL, Gabrielle VD, Jin L (2015) The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in\u00a0vivo. Elife 4: e06670","journal-title":"Elife"},{"key":"BFEMBR202152447_CR4","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.3389\/fimmu.2017.01772","volume":"8","author":"F Borriello","year":"2017","unstructured":"Borriello F, Pietrasanta C, Lai JCY, Walsh LM, Sharma P, O\u2019Driscoll DN, Ramirez J, Brightman S, Pugni L, Mosca F et\u00a0al (2017) Identification and characterization of stimulator of interferon genes as a robust adjuvant target for early life immunization. Front Immunol 8: 1772","journal-title":"Front Immunol"},{"key":"BFEMBR202152447_CR5","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1128\/jvi.68.9.6103-6110.1994","volume":"68","author":"P Borrow","year":"1994","unstructured":"Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB (1994) Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68: 6103\u20136110","journal-title":"J Virol"},{"key":"BFEMBR202152447_CR6","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1126\/science.aab3632","volume":"349","author":"A Bridgeman","year":"2015","unstructured":"Bridgeman A, Maelfait J, Davenne T, Partridge T, Peng Y, Mayer A, Dong T, Kaever V, Borrow P, Rehwinkel J (2015) Viruses transfer the antiviral second messenger cGAMP between cells. Science 349: 1228\u20131232","journal-title":"Science"},{"key":"BFEMBR202152447_CR7","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nature10429","volume":"478","author":"DL Burdette","year":"2011","unstructured":"Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, Hayakawa Y, Vance RE (2011) STING is a direct innate immune sensor of cyclic di-GMP. Nature 478: 515\u2013518","journal-title":"Nature"},{"key":"BFEMBR202152447_CR8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.molcel.2014.03.040","volume":"54","author":"X Cai","year":"2014","unstructured":"Cai X, Chiu YH, Chen ZJ (2014) The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol Cell 54: 289\u2013296","journal-title":"Mol Cell"},{"key":"BFEMBR202152447_CR9","doi-asserted-by":"crossref","first-page":"459","DOI":"10.5694\/mja2.50569","volume":"212","author":"L Caly","year":"2020","unstructured":"Caly L, Druce J, Roberts J, Bond K, Tran T, Kostecki R, Yoga Y, Naughton W, Taiaroa G, Seemann T et\u00a0al (2020) Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia. Med J Aust 212: 459\u2013462","journal-title":"Med J Aust"},{"key":"BFEMBR202152447_CR10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s43018-020-0028-4","volume":"1","author":"JA Carozza","year":"2020","unstructured":"Carozza JA, B\u00f6hnert V, Nguyen KC, Skariah G, Shaw KE, Brown JA, Rafat M, von Eyben R, Graves EE, Glenn JS et\u00a0al (2020) Extracellular cGAMP is a cancer-cell-produced immunotransmitter involved in radiation-induced anticancer immunity. Nature Cancer 1: 184\u2013196","journal-title":"Nature Cancer"},{"key":"BFEMBR202152447_CR11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jconrel.2018.09.020","volume":"289","author":"N Chen","year":"2018","unstructured":"Chen N, Gallovic MD, Tiet P, Ting JP, Ainslie KM, Bachelder EM (2018) Investigation of tunable acetalated dextran microparticle platform to optimize M2e-based influenza vaccine efficacy. J Control Release 289: 114\u2013124","journal-title":"J Control Release"},{"key":"BFEMBR202152447_CR12","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","volume":"33","author":"RL Coffman","year":"2010","unstructured":"Coffman RL, Sher A, Seder RA (2010) Vaccine adjuvants: putting innate immunity to work. Immunity 33: 492\u2013503","journal-title":"Immunity"},{"key":"BFEMBR202152447_CR13","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.celrep.2015.04.031","volume":"11","author":"L Corrales","year":"2015","unstructured":"Corrales L, Glickman L, McWhirter S, Kanne D, Sivick K, Katibah G, Woo S-R, Lemmens E, Banda T, Leong J et\u00a0al (2015) Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep 11: 1018\u20131030","journal-title":"Cell Rep"},{"key":"BFEMBR202152447_CR14","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","volume":"50","author":"S Crotty","year":"2019","unstructured":"Crotty S (2019) T follicular helper cell biology: a decade of discovery and diseases. Immunity 50: 1132\u20131148","journal-title":"Immunity"},{"key":"BFEMBR202152447_CR15","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.immuni.2009.07.005","volume":"31","author":"H Cucak","year":"2009","unstructured":"Cucak H, Yrlid U, Reizis B, Kalinke U, Johansson-Lindbom B (2009) Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells. Immunity 31: 491\u2013501","journal-title":"Immunity"},{"key":"BFEMBR202152447_CR16","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.cell.2019.03.016","volume":"177","author":"JG Cyster","year":"2019","unstructured":"Cyster JG, Allen CDC (2019) B cell responses: cell interaction dynamics and decisions. Cell 177: 524\u2013540","journal-title":"Cell"},{"key":"BFEMBR202152447_CR17","doi-asserted-by":"crossref","first-page":"15408","DOI":"10.1073\/pnas.1512832112","volume":"112","author":"O Demaria","year":"2015","unstructured":"Demaria O, De Gassart A, Coso S, Gestermann N, Di Domizio J, Flatz L, Gaide O, Michielin O, Hwu P, Petrova TV et\u00a0al (2015) STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity. Proc Natl Acad Sci USA 112: 15408\u201315413","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202152447_CR18","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.molimm.2004.06.028","volume":"42","author":"L Deml","year":"2005","unstructured":"Deml L, Speth C, Dierich MP, Wolf H, Wagner R (2005) Recombinant HIV-1 Pr55gag virus-like particles: potent stimulators of innate and acquired immune responses. Mol Immunol 42: 259\u2013277","journal-title":"Mol Immunol"},{"key":"BFEMBR202152447_CR19","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/j.celrep.2013.05.009","volume":"3","author":"EJ Diner","year":"2013","unstructured":"Diner EJ, Burdette DL, Wilson SC, Monroe KM, Kellenberger CA, Hyodo M, Hayakawa Y, Hammond MC, Vance RE (2013) The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep 3: 1355\u20131361","journal-title":"Cell Rep"},{"key":"BFEMBR202152447_CR20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/2051013613501988","volume":"1","author":"TW Dubensky Jr","year":"2013","unstructured":"Dubensky Jr TW, Kanne DB, Leong ML (2013) Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants. Ther Adv Vaccines 1: 131\u2013143","journal-title":"Ther Adv Vaccines"},{"key":"BFEMBR202152447_CR21","doi-asserted-by":"crossref","first-page":"5210","DOI":"10.1016\/j.vaccine.2011.05.026","volume":"29","author":"T Ebensen","year":"2011","unstructured":"Ebensen T, Libanova R, Schulze K, Yevsa T, Morr M, Guzman CA (2011) Bis-(3',5')-cyclic dimeric adenosine monophosphate: strong Th1\/Th2\/Th17 promoting mucosal adjuvant. Vaccine 29: 5210\u20135220","journal-title":"Vaccine"},{"key":"BFEMBR202152447_CR22","doi-asserted-by":"crossref","first-page":"7306","DOI":"10.1073\/pnas.1214441110","volume":"110","author":"D Finkelshtein","year":"2013","unstructured":"Finkelshtein D, Werman A, Novick D, Barak S, Rubinstein M (2013) LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc Natl Acad Sci USA 110: 7306\u20137311","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202152447_CR23","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.cell.2013.04.046","volume":"153","author":"Pu Gao","year":"2013","unstructured":"Gao Pu, Ascano M, Wu Y, Barchet W, Gaffney B, Zillinger T, Serganov A, Liu Y, Jones R, Hartmann G et\u00a0al (2013) Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell 153: 1094\u20131107","journal-title":"Cell"},{"key":"BFEMBR202152447_CR24","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1126\/science.aab3628","volume":"349","author":"M Gentili","year":"2015","unstructured":"Gentili M, Kowal J, Tkach M, Satoh T, Lahaye X, Conrad C, Boyron M, Lombard B, Durand S, Kroemer G et\u00a0al (2015) Transmission of innate immune signaling by packaging of cGAMP in viral particles. Science 349: 1232\u20131236","journal-title":"Science"},{"key":"BFEMBR202152447_CR25","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.125107","volume":"4","author":"A Gutjahr","year":"2019","unstructured":"Gutjahr A, Papagno L, Nicoli F, Kanuma T, Kuse N, Cabral-Piccin MP, Rochereau N, Gostick E, Lioux T, Perouzel E et\u00a0al (2019) The STING ligand cGAMP potentiates the efficacy of vaccine-induced CD8+ T cells. JCI Insight 4: e125107","journal-title":"JCI Insight"},{"key":"BFEMBR202152447_CR26","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature10003","volume":"473","author":"SG Hansen","year":"2011","unstructured":"Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson T et\u00a0al (2011) Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473: 523\u2013527","journal-title":"Nature"},{"key":"BFEMBR202152447_CR27","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1172\/JCI79915","volume":"125","author":"MC Hanson","year":"2015","unstructured":"Hanson MC, Crespo MP, Abraham W, Moynihan KD, Szeto GL, Chen SH, Melo MB, Mueller S, Irvine DJ (2015) Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants. J Clin Investig 125: 2532\u20132546","journal-title":"J Clin Investig"},{"key":"BFEMBR202152447_CR28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.virusres.2013.06.003","volume":"176","author":"E Hastie","year":"2013","unstructured":"Hastie E, Cataldi M, Marriott I, Grdzelishvili VZ (2013) Understanding and altering cell tropism of vesicular stomatitis virus. Virus Res 176: 16\u201332","journal-title":"Virus Res"},{"key":"BFEMBR202152447_CR29","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.molcel.2020.04.022","volume":"78","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Pohlmann S (2020) A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell 78: 779\u2013784.e5","journal-title":"Mol Cell"},{"key":"BFEMBR202152447_CR30","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.1016\/j.vaccine.2016.09.013","volume":"34","author":"SA Holechek","year":"2016","unstructured":"Holechek SA, McAfee MS, Nieves LM, Guzman VP, Manhas K, Fouts T, Bagley K, Blattman JN (2016) Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination. Vaccine 34: 5629\u20135635","journal-title":"Vaccine"},{"key":"BFEMBR202152447_CR31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.immuni.2018.08.012","volume":"49","author":"S Hong","year":"2018","unstructured":"Hong S, Zhang Z, Liu H, Tian M, Zhu X, Zhang Z, Wang W, Zhou X, Zhang F, Ge Q et\u00a0al (2018) B cells are the dominant antigen-presenting cells that activate naive CD4(+) T cells upon immunization with a virus-derived nanoparticle antigen. Immunity 49: 695\u2013708.e4","journal-title":"Immunity"},{"key":"BFEMBR202152447_CR32","volume":"17","author":"KA Huang","year":"2021","unstructured":"Huang KA, Tan TK, Chen TH, Huang CG, Harvey R, Hussain S, Chen CP, Harding A, Gilbert-Jaramillo J, Liu X et\u00a0al (2021) Breadth and function of antibody response to acute SARS-CoV-2 infection in humans. PLoS Pathog 17: e1009352","journal-title":"PLoS Pathog"},{"key":"BFEMBR202152447_CR33","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/ni957","volume":"4","author":"AA Itano","year":"2003","unstructured":"Itano AA, Jenkins MK (2003) Antigen presentation to naive CD4 T cells in the lymph node. Nat Immunol 4: 733\u2013739","journal-title":"Nat Immunol"},{"key":"BFEMBR202152447_CR34","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.4049\/jimmunol.1100088","volume":"187","author":"L Jin","year":"2011","unstructured":"Jin L, Hill KK, Filak H, Mogan J, Knowles H, Zhang B, Perraud AL, Cambier JC, Lenz LL (2011) MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol 187: 2595\u20132601","journal-title":"J Immunol"},{"key":"BFEMBR202152447_CR35","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1600-065X.2008.00718.x","volume":"227","author":"O Joffre","year":"2009","unstructured":"Joffre O, Nolte MA, Sporri R, Reis e Sousa C (2009) Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunol Rev 227: 234\u2013247","journal-title":"Immunol Rev"},{"key":"BFEMBR202152447_CR36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2017.11.030","volume":"270","author":"RD Junkins","year":"2018","unstructured":"Junkins RD, Gallovic MD, Johnson BM, Collier MA, Watkins-Schulz R, Cheng N, David CN, McGee CE, Sempowski GD, Shterev I et\u00a0al (2018) A robust microparticle platform for a STING-targeted adjuvant that enhances both humoral and cellular immunity during vaccination. J Control Release 270: 1\u201313","journal-title":"J Control Release"},{"key":"BFEMBR202152447_CR37","doi-asserted-by":"crossref","first-page":"8964","DOI":"10.1073\/pnas.86.22.8964","volume":"86","author":"V Karacostas","year":"1989","unstructured":"Karacostas V, Nagashima K, Gonda MA, Moss B (1989) Human immunodeficiency virus-like particles produced by a vaccinia virus expression vector. Proc Natl Acad Sci USA 86: 8964\u20138967","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202152447_CR38","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41577-019-0143-6","volume":"19","author":"F Krammer","year":"2019","unstructured":"Krammer F (2019) The human antibody response to influenza A virus infection and vaccination. Nat Rev Immunol 19: 383\u2013397","journal-title":"Nat Rev Immunol"},{"key":"BFEMBR202152447_CR39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ebiom.2019.03.078","volume":"42","author":"N Kuse","year":"2019","unstructured":"Kuse N, Sun X, Akahoshi T, Lissina A, Yamamoto T, Appay V, Takiguchi M (2019) Priming of HIV-1-specific CD8(+) T cells with strong functional properties from naive T cells. EBioMedicine 42: 109\u2013119","journal-title":"EBioMedicine"},{"key":"BFEMBR202152447_CR40","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.actbio.2015.10.025","volume":"29","author":"E Lee","year":"2016","unstructured":"Lee E, Jang HE, Kang YY, Kim J, Ahn JH, Mok H (2016) Submicron-sized hydrogels incorporating cyclic dinucleotides for selective delivery and elevated cytokine release in macrophages. Acta Biomater 29: 271\u2013281","journal-title":"Acta Biomater"},{"key":"BFEMBR202152447_CR41","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nchembio.1661","volume":"10","author":"L Li","year":"2014","unstructured":"Li L, Yin Q, Kuss P, Maliga Z, Millan JL, Wu H, Mitchison TJ (2014) Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs. Nat Chem Biol 10: 1043\u20131048","journal-title":"Nat Chem Biol"},{"key":"BFEMBR202152447_CR42","doi-asserted-by":"crossref","first-page":"19049","DOI":"10.1038\/srep19049","volume":"6","author":"T Li","year":"2016","unstructured":"Li T, Cheng H, Yuan H, Xu Q, Shu C, Zhang Y, Xu P, Tan J, Rui Y, Li P et\u00a0al (2016) Antitumor activity of cGAMP via stimulation of cGAS-cGAMP-STING-IRF3 mediated innate immune response. Sci Rep 6: 19049","journal-title":"Sci Rep"},{"key":"BFEMBR202152447_CR43","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1126\/science.1244040","volume":"341","author":"XD Li","year":"2013","unstructured":"Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ (2013) Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science 341: 1390\u20131394","journal-title":"Science"},{"key":"BFEMBR202152447_CR44","doi-asserted-by":"crossref","first-page":"88","DOI":"10.12688\/f1000research.7388.1","volume":"5","author":"MA Linterman","year":"2016","unstructured":"Linterman MA, Hill DL (2016) Can follicular helper T cells be targeted to improve vaccine efficacy? F1000Res 5: 88","journal-title":"F1000Res"},{"key":"BFEMBR202152447_CR45","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/abbs\/gmw078","volume":"48","author":"Y Liu","year":"2016","unstructured":"Liu Y, Chen S, Pan B, Guan Z, Yang Z, Duan L, Cai H (2016) A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages. Acta Biochim Biophys Sin 48: 909\u2013922","journal-title":"Acta Biochim Biophys Sin"},{"key":"BFEMBR202152447_CR46","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.3389\/fimmu.2019.02274","volume":"10","author":"J Luo","year":"2019","unstructured":"Luo J, Liu XP, Xiong FF, Gao FX, Yi YL, Zhang M, Chen Z, Tan WS (2019) Enhancing immune response and heterosubtypic protection ability of inactivated H7N9 vaccine by using STING agonist as a mucosal adjuvant. Front Immunol 10: 2274","journal-title":"Front Immunol"},{"key":"BFEMBR202152447_CR47","doi-asserted-by":"crossref","first-page":"8418","DOI":"10.1128\/JVI.77.15.8418-8425.2003","volume":"77","author":"M Matrosovich","year":"2003","unstructured":"Matrosovich M, Matrosovich T, Carr J, Roberts NA, Klenk HD (2003) Overexpression of the alpha-2,6-sialyltransferase in MDCK cells increases influenza virus sensitivity to neuraminidase inhibitors. J Virol 77: 8418\u20138425","journal-title":"J Virol"},{"key":"BFEMBR202152447_CR48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-4939-7237-1_8","volume":"1656","author":"A Mayer","year":"2017","unstructured":"Mayer A, Maelfait J, Bridgeman A, Rehwinkel J (2017) Purification of cyclic GMP-AMP from viruses and measurement of its activity in cell culture. Methods Mol Biol 1656: 143\u2013152","journal-title":"Methods Mol Biol"},{"key":"BFEMBR202152447_CR49","doi-asserted-by":"crossref","first-page":"16017","DOI":"10.1038\/mtm.2016.17","volume":"3","author":"OW Merten","year":"2016","unstructured":"Merten OW, Hebben M, Bovolenta C (2016) Production of lentiviral vectors. Mol Ther Methods Clin Dev 3: 16017","journal-title":"Mol Ther Methods Clin Dev"},{"key":"BFEMBR202152447_CR50","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/s41375-018-0106-0","volume":"32","author":"MC Milone","year":"2018","unstructured":"Milone MC, O'Doherty U (2018) Clinical use of lentiviral vectors. Leukemia 32: 1529\u20131541","journal-title":"Leukemia"},{"key":"BFEMBR202152447_CR51","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jconrel.2017.02.031","volume":"251","author":"MO Mohsen","year":"2017","unstructured":"Mohsen MO, Gomes AC, Cabral-Miranda G, Krueger CC, Leoratti FM, Stein JV, Bachmann MF (2017) Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination. J Control Release 251: 92\u2013100","journal-title":"J Control Release"},{"key":"BFEMBR202152447_CR52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13073-016-0288-x","volume":"8","author":"M Nielsen","year":"2016","unstructured":"Nielsen M, Andreatta M (2016) NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets. Genome Med 8: 33","journal-title":"Genome Med"},{"key":"BFEMBR202152447_CR53","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.1176676","volume":"325","author":"RI Nurieva","year":"2009","unstructured":"Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C (2009) Bcl6 mediates the development of T follicular helper cells. Science 325: 1001\u20131005","journal-title":"Science"},{"key":"BFEMBR202152447_CR54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1074-7613(00)80533-6","volume":"8","author":"A O'Garra","year":"1998","unstructured":"O'Garra A (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8: 275\u2013283","journal-title":"Immunity"},{"key":"BFEMBR202152447_CR55","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-1-4615-1823-5_10","volume":"6","author":"G Ott","year":"1995","unstructured":"Ott G, Barchfeld GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G (1995) MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol 6: 277\u2013296","journal-title":"Pharm Biotechnol"},{"key":"BFEMBR202152447_CR56","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fimmu.2018.00276","volume":"9","author":"E Panagioti","year":"2018","unstructured":"Panagioti E, Klenerman P, Lee LN, van der Burg SH, Arens R (2018) Features of effective T cell-inducing vaccines against chronic viral infections. Front Immunol 9: 276","journal-title":"Front Immunol"},{"key":"BFEMBR202152447_CR57","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.tim.2015.07.005","volume":"23","author":"M Pelegrin","year":"2015","unstructured":"Pelegrin M, Naranjo-Gomez M, Piechaczyk M (2015) Antiviral monoclonal antibodies: can they be more than simple neutralizing agents? Trends Microbiol 23: 653\u2013665","journal-title":"Trends Microbiol"},{"key":"BFEMBR202152447_CR58","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1128\/JVI.01818-06","volume":"81","author":"A Pichlmair","year":"2007","unstructured":"Pichlmair A, Diebold SS, Gschmeissner S, Takeuchi Y, Ikeda Y, Collins MK, Reis e Sousa C (2007) Tubulovesicular structures within vesicular stomatitis virus G protein-pseudotyped lentiviral vector preparations carry DNA and stimulate antiviral responses via Toll-like receptor 9. J Virol 81: 539\u2013547","journal-title":"J Virol"},{"key":"BFEMBR202152447_CR59","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1128\/JVI.01820-12","volume":"86","author":"TJ Powell","year":"2012","unstructured":"Powell TJ, Silk JD, Sharps J, Fodor E, Townsend AR (2012) Pseudotyped influenza A virus as a vaccine for the induction of heterotypic immunity. J Virol 86: 13397\u201313406","journal-title":"J Virol"},{"key":"BFEMBR202152447_CR60","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nri3085","volume":"11","author":"R Rappuoli","year":"2011","unstructured":"Rappuoli R, Mandl CW, Black S, De Gregorio E (2011) Vaccines for the twenty-first century society. Nat Rev Immunol 11: 865\u2013872","journal-title":"Nat Rev Immunol"},{"key":"BFEMBR202152447_CR61","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints 12. Am J Epidemiol 27: 493\u2013497","journal-title":"Am J Epidemiol"},{"key":"BFEMBR202152447_CR62","doi-asserted-by":"crossref","first-page":"3884","DOI":"10.4049\/jimmunol.1600883","volume":"197","author":"N Riteau","year":"2016","unstructured":"Riteau N, Radtke AJ, Shenderov K, Mittereder L, Oland SD, Hieny S, Jankovic D, Sher A (2016) Water-in-oil-only adjuvants selectively promote T follicular helper cell polarization through a type I IFN and IL-6-dependent pathway. J Immunol 197: 3884\u20133893","journal-title":"J Immunol"},{"key":"BFEMBR202152447_CR63","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ni.2496","volume":"14","author":"PT Sage","year":"2013","unstructured":"Sage PT, Francisco LM, Carman CV, Sharpe AH (2013) The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nat Immunol 14: 152\u2013161","journal-title":"Nat Immunol"},{"key":"BFEMBR202152447_CR64","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/j.vaccine.2019.04.055","volume":"37","author":"S Shi","year":"2019","unstructured":"Shi S, Zhu H, Xia X, Liang Z, Ma X, Sun B (2019) Vaccine adjuvants: Understanding the structure and mechanism of adjuvanticity. Vaccine 37: 3167\u20133178","journal-title":"Vaccine"},{"key":"BFEMBR202152447_CR65","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","volume":"339","author":"L Sun","year":"2013","unstructured":"Sun L, Wu J, Du F, Chen X, Chen ZJ (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339: 786\u2013791","journal-title":"Science"},{"key":"BFEMBR202152447_CR66","doi-asserted-by":"crossref","first-page":"35","DOI":"10.29387\/ms.2017.5.3.35-36","volume":"5","author":"H Takaki","year":"2017","unstructured":"Takaki H, Takashima K, Oshiumi H, Ainai A, Suzuki T, Hasegawa H, Matsumoto M, Seya T (2017) cGAMP promotes germinal center formation and production of IgA in nasal-associated lymphoid tissue. Med Sci 5: 35","journal-title":"Med Sci"},{"key":"BFEMBR202152447_CR67","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1002\/eji.201445132","volume":"45","author":"B Temizoz","year":"2015","unstructured":"Temizoz B, Kuroda E, Ohata K, Jounai N, Ozasa K, Kobiyama K, Aoshi T, Ishii KJ (2015) TLR9 and STING agonists synergistically induce innate and adaptive type-II IFN. Eur J Immunol 45: 1159\u20131169","journal-title":"Eur J Immunol"},{"key":"BFEMBR202152447_CR68","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.coph.2018.05.003","volume":"41","author":"B Temizoz","year":"2018","unstructured":"Temizoz B, Kuroda E, Ishii KJ (2018) Combination and inducible adjuvants targeting nucleic acid sensors. Curr Opin Pharmacol 41: 104\u2013113","journal-title":"Curr Opin Pharmacol"},{"key":"BFEMBR202152447_CR69","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1084\/jem.20052005","volume":"203","author":"C Trumpfheller","year":"2006","unstructured":"Trumpfheller C, Finke JS, Lo\u00f3pez CB, Moran TM, Moltedo B, Soares H, Huang Y, Schlesinger SJ, Park CG, Nussenzweig MC et\u00a0al (2006) Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J Exp Med 203: 607\u2013617","journal-title":"J Exp Med"},{"key":"BFEMBR202152447_CR70","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.3389\/fimmu.2019.03006","volume":"10","author":"EV Vassilieva","year":"2019","unstructured":"Vassilieva EV, Taylor DW, Compans RW (2019) Combination of STING pathway agonist with saponin is an effective adjuvant in immunosenescent mice. Front Immunol 10: 3006","journal-title":"Front Immunol"},{"key":"BFEMBR202152447_CR71","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1073\/pnas.1621363114","volume":"114","author":"H Wang","year":"2017","unstructured":"Wang H, Hu S, Chen X, Shi H, Chen C, Sun L, Chen ZJ (2017) cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc Natl Acad Sci USA 114: 1637\u20131642","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202152447_CR72","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.jid.2016.05.105","volume":"136","author":"J Wang","year":"2016","unstructured":"Wang J, Li P, Wu MX (2016) Natural STING agonist as an \"Ideal\" adjuvant for cutaneous vaccination. J Invest Dermatol 136: 2183\u20132191","journal-title":"J Invest Dermatol"},{"key":"BFEMBR202152447_CR73","doi-asserted-by":"crossref","first-page":"eaau0810","DOI":"10.1126\/science.aau0810","volume":"367","author":"J Wang","year":"2020","unstructured":"Wang J, Li P, Yu Y, Fu Y, Jiang H, Lu M, Sun Z, Jiang S, Lu L, Wu MX (2020) Pulmonary surfactant-biomimetic nanoparticles potentiate heterosubtypic influenza immunity. Science 367: eaau0810","journal-title":"Science"},{"key":"BFEMBR202152447_CR74","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/292072a0","volume":"292","author":"G Winter","year":"1981","unstructured":"Winter G, Fields S, Brownlee GG (1981) Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype. Nature 292: 72\u201375","journal-title":"Nature"},{"key":"BFEMBR202152447_CR75","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1126\/science.1229963","volume":"339","author":"J Wu","year":"2013","unstructured":"Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ (2013) Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339: 826\u2013830","journal-title":"Science"},{"key":"BFEMBR202152447_CR76","volume":"92","author":"JH Xiao","year":"2018","unstructured":"Xiao JH, Rijal P, Schimanski L, Tharkeshwar AK, Wright E, Annaert W, Townsend A (2018) Characterization of influenza virus pseudotyped with ebolavirus glycoprotein. J Virol 92: e00941-17","journal-title":"J Virol"},{"key":"BFEMBR202152447_CR77","doi-asserted-by":"crossref","first-page":"6265","DOI":"10.4049\/jimmunol.172.10.6265","volume":"172","author":"R Xu","year":"2004","unstructured":"Xu R, Johnson AJ, Liggitt D, Bevan MJ (2004) Cellular and humoral immunity against vaccinia virus infection of mice. J Immunol 172: 6265\u20136271","journal-title":"J Immunol"},{"key":"BFEMBR202152447_CR78","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nbt1390","volume":"26","author":"L Yang","year":"2008","unstructured":"Yang L, Yang H, Rideout K, Cho T, Joo Ki, Ziegler L, Elliot A, Walls A, Yu D, Baltimore D et\u00a0al (2008) Engineered lentivector targeting of dendritic cells for in\u00a0vivo immunization. Nat Biotechnol 26: 326\u2013334","journal-title":"Nat Biotechnol"},{"key":"BFEMBR202152447_CR79","volume":"8","author":"G Yi","year":"2013","unstructured":"Yi G, Brendel VP, Shu C, Li P, Palanathan S, Cheng Kao C (2013) Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides. PLoS One 8: e77846","journal-title":"PLoS One"},{"key":"BFEMBR202152447_CR80","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.molcel.2013.05.022","volume":"51","author":"X Zhang","year":"2013","unstructured":"Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, Chen ZJ (2013) Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell 51: 226\u2013235","journal-title":"Mol Cell"},{"key":"BFEMBR202152447_CR81","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/s41594-020-0480-y","volume":"27","author":"D Zhou","year":"2020","unstructured":"Zhou D, Duyvesteyn HME, Chen C-P, Huang C-G, Chen T-H, Shih S-R, Lin Y-C, Cheng C-Y, Cheng S-H, Huang Y-C et\u00a0al (2020) Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nat Struct Mol Biol 27: 950\u2013958","journal-title":"Nat Struct Mol Biol"}],"container-title":["The EMBO Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.202152447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embr.202152447","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embr.202152447\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embr.202152447","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.202152447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:51:50Z","timestamp":1779112310000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embr.202152447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":81,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8,4]]}},"alternative-id":["BFEMBR202152447"],"URL":"https:\/\/doi.org\/10.15252\/embr.202152447","relation":{},"ISSN":["1469-221X","1469-3178"],"issn-type":[{"value":"1469-221X","type":"print"},{"value":"1469-3178","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,18]]},"assertion":[{"value":"12 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMBR202152447"}}