{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T09:49:54Z","timestamp":1783763394603,"version":"3.55.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T00:00:00Z","timestamp":1469059200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T00:00:00Z","timestamp":1469059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although glycoconjugate vaccines are generally very efficacious, there is still a need to improve their efficacy, especially in eliciting a strong primary antibody response. We have recently described a new type of vaccine adjuvant based on a TLR7 agonist adsorbed to alum (Alum-TLR7), which is highly efficacious at enhancing immunogenicity of protein based vaccines. Since no adjuvant has been shown to potentiate the immune response to glycoconjugate vaccines in humans, we investigated if Alum-TLR7 is able to improve immunogenicity of this class of vaccines. We found that in a mouse model Alum-TLR7 greatly improved potency of a CRM<jats:sub>197<\/jats:sub>-MenC vaccine increasing anti-MenC antibody titers and serum bactericidal activity (SBA) against MenC compared to alum adjuvanted vaccine, especially with a low dose of antigen and already after a single immunization. Alum-TLR7 also drives antibody response towards Th1 isotypes. This adjuvant was also able to increase immunogenicity of all polysaccharides of a multicomponent glycoconjugate vaccine CRM<jats:sub>197<\/jats:sub>-MenACWY. Furthermore, we found that Alum-TLR7 increases anti-polysaccharide immune response even in the presence of a prior immune response against the carrier protein. Finally, we demonstrate that Alum-TLR7 adjuvant effect requires a functional TLR7. Taken together, our data support the use of Alum-TLR7 as adjuvant for glycoconjugate vaccines.<\/jats:p>","DOI":"10.1038\/srep29063","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T09:13:29Z","timestamp":1469092409000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines"],"prefix":"10.1038","volume":"6","author":[{"given":"Cecilia","family":"Buonsanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Balocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Harfouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Corrente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Galli Stampino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Tontini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padma","family":"Malyala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Bufali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Baudner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"De Gregorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Valiante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek T.","family":"O\u2019Hagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rino","family":"Rappuoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"D\u2019Oro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,21]]},"reference":[{"key":"BFsrep29063_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nri3694","volume":"14","author":"E De Gregorio","year":"2014","unstructured":"De Gregorio, E. & Rappuoli, R. From empiricism to rational design: a personal perspective of the evolution of vaccine development. Nature reviews. Immunology 14, 505\u2013514, doi: 10.1038\/nri3694 (2014).","journal-title":"Nature reviews. Immunology"},{"key":"BFsrep29063_CR2","doi-asserted-by":"publisher","first-page":"4434","DOI":"10.1016\/j.vaccine.2008.05.073","volume":"26","author":"CL Trotter","year":"2008","unstructured":"Trotter, C. L. et al. Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae. Vaccine 26, 4434\u20134445, doi: 10.1016\/j.vaccine.2008.05.073 (2008).","journal-title":"Vaccine"},{"key":"BFsrep29063_CR3","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1517\/17460441.2011.609554","volume":"6","author":"P Costantino","year":"2011","unstructured":"Costantino, P., Rappuoli, R. & Berti, F. The design of semi-synthetic and synthetic glycoconjugate vaccines. Expert Opinion on Drug Discovery 6, 1045\u20131066, doi: 10.1517\/17460441.2011.609554 (2011).","journal-title":"Expert Opinion on Drug Discovery"},{"key":"BFsrep29063_CR4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1146\/annurev-immunol-030409-101159","volume":"28","author":"FY Avci","year":"2010","unstructured":"Avci, F. Y. & Kasper, D. L. How bacterial carbohydrates influence the adaptive immune system. Annual Review of Immunology 28, 107\u2013130, doi: 10.1146\/annurev-immunol-030409-101159 (2010).","journal-title":"Annual Review of Immunology"},{"key":"BFsrep29063_CR5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1517\/14712598.2013.748030","volume":"13","author":"G Del Giudice","year":"2013","unstructured":"Del Giudice, G., Fragapane, E., Della Cioppa, G. & Rappuoli, R. Aflunov (R): a vaccine tailored for pre-pandemic and pandemic approaches against influenza. Expert Opinion on Biological Therapy 13, 121\u2013135, doi: 10.1517\/14712598.2013.748030 (2013).","journal-title":"Expert Opinion on Biological Therapy"},{"key":"BFsrep29063_CR6","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/ni.2039","volume":"12","author":"B Pulendran","year":"2011","unstructured":"Pulendran, B. & Ahmed, R. Immunological mechanisms of vaccination. Nature Immunology 12, 509\u2013517 (2011).","journal-title":"Nature Immunology"},{"key":"BFsrep29063_CR7","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1056\/NEJMoa1010331","volume":"365","author":"T Vesikari","year":"2011","unstructured":"Vesikari, T. et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. The New England journal of Medicine 365, 1406\u20131416, doi: 10.1056\/NEJMoa1010331 (2011).","journal-title":"The New England journal of Medicine"},{"key":"BFsrep29063_CR8","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1586\/erv.11.192","volume":"11","author":"N Garcon","year":"2012","unstructured":"Garcon, N., Vaughn, D. W. & Didierlaurent, A. M. Development and evaluation of AS03, an Adjuvant System containing alpha-tocopherol and squalene in an oil-in-water emulsion. Expert Review of Vaccines 11, 349\u2013366, doi: 10.1586\/erv.11.192 (2012).","journal-title":"Expert Review of Vaccines"},{"key":"BFsrep29063_CR9","doi-asserted-by":"publisher","first-page":"217","DOI":"10.2165\/11591760-000000000-00000","volume":"25","author":"N Garcon","year":"2011","unstructured":"Garcon, N. et al. Development of an AS04-adjuvanted HPV vaccine with the adjuvant system approach. BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy 25, 217\u2013226, doi: 10.2165\/11591760-000000000-00000 (2011).","journal-title":"BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy"},{"key":"BFsrep29063_CR10","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1111\/j.1600-065X.2010.00978.x","volume":"239","author":"MS Duthie","year":"2011","unstructured":"Duthie, M. S., Windish, H. P., Fox, C. B. & Reed, S. G. Use of defined TLR ligands as adjuvants within human vaccines. Immunological Reviews 239, 178\u2013196, doi: 10.1111\/j.1600-065X.2010.00978.x (2011).","journal-title":"Immunological Reviews"},{"key":"BFsrep29063_CR11","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/sj.ki.5002725","volume":"73","author":"NC Kong","year":"2008","unstructured":"Kong, N. C. et al. A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients. Kidney International 73, 856\u2013862, doi: 10.1038\/sj.ki.5002725 (2008).","journal-title":"Kidney International"},{"key":"BFsrep29063_CR12","doi-asserted-by":"publisher","first-page":"263ra160","DOI":"10.1126\/scitranslmed.3009980","volume":"6","author":"TY Wu","year":"2014","unstructured":"Wu, T. Y. et al. Rational design of small molecules as vaccine adjuvants. Science Translational Medicine 6, 263ra160, doi: 10.1126\/scitranslmed.3009980 (2014).","journal-title":"Science Translational Medicine"},{"key":"BFsrep29063_CR13","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1080\/21645515.2015.1011021","volume":"11","author":"J Levy","year":"2015","unstructured":"Levy, J. et al. Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial. Human Vaccines & Immunotherapeutics 11, 620\u2013631, doi: 10.1080\/21645515.2015.1011021 (2015).","journal-title":"Human Vaccines & Immunotherapeutics"},{"key":"BFsrep29063_CR14","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jinf.2012.09.008","volume":"66","author":"W Hellenbrand","year":"2013","unstructured":"Hellenbrand, W. et al. Epidemiology of invasive meningococcal disease in Germany, 2002-2010, and impact of vaccination with meningococcal C conjugate vaccine. The Journal of Infection 66, 48\u201356, doi: 10.1016\/j.jinf.2012.09.008 (2013).","journal-title":"The Journal of Infection"},{"key":"BFsrep29063_CR15","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1146\/annurev.iy.08.040190.001511","volume":"8","author":"FD Finkelman","year":"1990","unstructured":"Finkelman, F. D. et al. Lymphokine control of in vivo immunoglobulin isotype selection. Annual Review of Immunology 8, 303\u2013333, doi: 10.1146\/annurev.iy.08.040190.001511 (1990).","journal-title":"Annual Review of Immunology"},{"key":"BFsrep29063_CR16","doi-asserted-by":"publisher","first-page":"4213","DOI":"10.4049\/jimmunol.1003585","volume":"186","author":"C Iavarone","year":"2011","unstructured":"Iavarone, C. et al. A point mutation in the amino terminus of TLR7 abolishes signaling without affecting ligand binding. Journal of Immunology 186, 4213\u20134222, doi: 10.4049\/jimmunol.1003585 (2011).","journal-title":"Journal of Immunology"},{"key":"BFsrep29063_CR17","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1086\/653112","volume":"51","author":"OS Sogaard","year":"2010","unstructured":"Sogaard, O. S. et al. Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial. Clinical Infectious Diseases: An Official Publication of The Infectious Diseases Society of America 51, 42\u201350, doi: 10.1086\/653112 (2010).","journal-title":"Clinical Infectious Diseases: An Official Publication of The Infectious Diseases Society of America"},{"key":"BFsrep29063_CR18","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/nrd1176","volume":"2","author":"DT O\u2019Hagan","year":"2003","unstructured":"O\u2019Hagan, D. T. & Valiante, N. M. Recent advances in the discovery and delivery of vaccine adjuvants. Nature Reviews. Drug discovery 2, 727\u2013735, doi: 10.1038\/nrd1176 (2003).","journal-title":"Nature Reviews. Drug discovery"},{"key":"BFsrep29063_CR19","doi-asserted-by":"publisher","first-page":"6186","DOI":"10.4049\/jimmunol.0901474","volume":"183","author":"AM Didierlaurent","year":"2009","unstructured":"Didierlaurent, A. M. et al. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. Journal of Immunology 183, 6186\u20136197, doi: 10.4049\/jimmunol.0901474 (2009).","journal-title":"Journal of Immunology"},{"key":"BFsrep29063_CR20","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nm0411-415","volume":"17","author":"ML Mbow","year":"2011","unstructured":"Mbow, M. L., De Gregorio, E. & Ulmer, J. B. Alum\u2019s adjuvant action: grease is the word. Nature Medicine 17, 415\u2013416, doi: 10.1038\/nm0411-415 (2011).","journal-title":"Nature Medicine"},{"key":"BFsrep29063_CR21","doi-asserted-by":"publisher","first-page":"e0147767","DOI":"10.1371\/journal.pone.0147767","volume":"11","author":"F Mancini","year":"2016","unstructured":"Mancini, F. et al. One Dose of Staphylococcus aureus 4C-Staph Vaccine Formulated with a Novel TLR7-Dependent Adjuvant Rapidly Protects Mice through Antibodies, Effector CD4+ T Cells, and IL-17A. PloS One 11, e0147767, doi: 10.1371\/journal.pone.0147767 (2016).","journal-title":"PloS One"},{"key":"BFsrep29063_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2015.04.006","volume":"60","author":"N Isailovic","year":"2015","unstructured":"Isailovic, N., Daigo, K., Mantovani, A. & Selmi, C. Interleukin-17 and innate immunity in infections and chronic inflammation. Journal of Autoimmunity 60, 1\u201311, doi: 10.1016\/j.jaut.2015.04.006 (2015).","journal-title":"Journal of Autoimmunity"},{"key":"BFsrep29063_CR23","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/nri2075","volume":"7","author":"O Levy","year":"2007","unstructured":"Levy, O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nature Reviews. Immunology 7, 379\u2013390, doi: 10.1038\/nri2075 (2007).","journal-title":"Nature Reviews. Immunology"},{"key":"BFsrep29063_CR24","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.immuni.2012.10.014","volume":"37","author":"TR Kollmann","year":"2012","unstructured":"Kollmann, T. R., Levy, O., Montgomery, R. R. & Goriely, S. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37, 771\u2013783, doi: 10.1016\/j.immuni.2012.10.014 (2012).","journal-title":"Immunity"},{"key":"BFsrep29063_CR25","doi-asserted-by":"publisher","first-page":"5513","DOI":"10.1016\/j.vaccine.2010.06.026","volume":"28","author":"R Dagan","year":"2010","unstructured":"Dagan, R., Poolman, J. & Siegrist, C. A. Glycoconjugate vaccines and immune interference: A review. Vaccine 28, 5513\u20135523, doi: 10.1016\/j.vaccine.2010.06.026 (2010).","journal-title":"Vaccine"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep29063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29063","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T05:33:31Z","timestamp":1672896811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep29063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,21]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,21]]}},"alternative-id":["BFsrep29063"],"URL":"https:\/\/doi.org\/10.1038\/srep29063","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,21]]},"assertion":[{"value":"21 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors are former or current employees or contractors of the GSK group of companies. PM, SB, EDG, NMV, DOH and RR owns Novartis\/GSK stocks. CrB, BB, PM, SB, NMV, DOH, RR and UD are listed as inventors on patents owned by the GSK group of companies. <i>Menjugate<\/i> and <i>Menveo<\/i> are trademarks of the GSK group of companies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29063"}}