{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:45:23Z","timestamp":1791895523085,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009169","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004784","name":"Novartis Stiftung\u00a0f\u00fcr\u00a0Medizinisch-Biologische Forschung","doi-asserted-by":"crossref","award":["19B116"],"award-info":[{"award-number":["19B116"]}],"id":[{"id":"10.13039\/501100004784","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable efforts in vaccine development, HCMV infection still represents an unmet clinical need. In recent phase II trials, a MF59-adjuvanted gB vaccine showed only modest efficacy in preventing infection. These findings might be attributed to low level of antibodies (Abs) with a neutralizing activity induced by this vaccine. Here, we analyzed the immunogenicity of each gB antigenic domain (AD) and demonstrated that domain I of gB (AD5) is the main target of HCMV neutralizing antibodies. Furthermore, we designed, characterized and evaluated immunogenic responses to two different nanoparticles displaying a trimeric AD5 antigen. We showed that mice immunization with nanoparticles induces sera neutralization titers up to 100-fold higher compared to those obtained with the gB extracellular domain (gB<jats:sub>ECD<\/jats:sub>). Collectively, these results illustrate with a medically relevant example the advantages of using a general approach combining antigen discovery, protein engineering and scaffold presentation for modern development of subunit vaccines against complex pathogens.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009169","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T20:07:01Z","timestamp":1609186021000},"page":"e1009169","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity"],"prefix":"10.1371","volume":"16","author":[{"given":"Michela","family":"Perotti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4723-6892","authenticated-orcid":true,"given":"Jessica","family":"Marcandalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Demurtas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Sallusto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8860-7928","authenticated-orcid":true,"given":"Laurent","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"issue":"4","key":"ppat.1009169.ref001","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review 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Thompson","year":"2018","journal-title":"Vaccine"},{"key":"ppat.1009169.ref011","article-title":"The structural basis of herpesvirus entry","author":"SA Connolly","year":"2020","journal-title":"Nature reviews Microbiology"},{"issue":"12","key":"ppat.1009169.ref012","doi-asserted-by":"crossref","DOI":"10.3390\/v10120704","article-title":"Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism","volume":"10","author":"CC Nguyen","year":"2018","journal-title":"Viruses"},{"key":"ppat.1009169.ref013","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.coviro.2018.05.004","article-title":"From recognition to execution-the HCMV Pentamer from receptor binding to fusion triggering","volume":"31","author":"E Malito","year":"2018","journal-title":"Current opinion in virology"},{"issue":"4","key":"ppat.1009169.ref014","doi-asserted-by":"crossref","first-page":"e1005564","DOI":"10.1371\/journal.ppat.1005564","article-title":"Human Cytomegalovirus gH\/gL Forms a Stable Complex with the Fusion Protein gB in Virions","volume":"12","author":"AL Vanarsdall","year":"2016","journal-title":"PLoS Pathog"},{"issue":"23","key":"ppat.1009169.ref015","doi-asserted-by":"crossref","first-page":"11837","DOI":"10.1128\/JVI.01623-08","article-title":"Human cytomegalovirus glycoproteins gB and gH\/gL mediate epithelial cell-cell fusion when expressed either in cis or in trans","volume":"82","author":"AL Vanarsdall","year":"2008","journal-title":"J Virol"},{"issue":"24","key":"ppat.1009169.ref016","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1073\/pnas.1800177115","article-title":"HCMV glycoprotein B subunit vaccine efficacy mediated by nonneutralizing antibody effector functions","volume":"115","author":"CS Nelson","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"ppat.1009169.ref017","doi-asserted-by":"crossref","first-page":"6273","DOI":"10.1073\/pnas.1800224115","article-title":"Protection from cytomegalovirus viremia 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Protection From Viremia","volume":"217","author":"I Baraniak","year":"2018","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1009169.ref039","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1128\/JVI.01809-09","article-title":"Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH\/gL\/UL128-131A complex","volume":"84","author":"A Macagno","year":"2010","journal-title":"J Virol"},{"issue":"7467","key":"ppat.1009169.ref040","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nature12442","article-title":"Cross-neutralization of four paramyxoviruses by a human monoclonal antibody","volume":"501","author":"D Corti","year":"2013","journal-title":"Nature"},{"issue":"2","key":"ppat.1009169.ref041","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bbapap.2005.06.005","article-title":"How to study proteins by circular dichroism","volume":"1751","author":"SM 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whereas gH\/gL\/UL128-131 Broadens Virus Tropism through a Distinct Mechanism","volume":"89","author":"M Zhou","year":"2015","journal-title":"J Virol"},{"issue":"42","key":"ppat.1009169.ref063","doi-asserted-by":"crossref","first-page":"E9889","DOI":"10.1073\/pnas.1806305115","article-title":"Role of PDGF receptor-\u03b1 during human cytomegalovirus entry into fibroblasts","volume":"115","author":"K Wu","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"Supplement_1","key":"ppat.1009169.ref064","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1093\/infdis\/jiz428","article-title":"Immune Correlates of Protection Against Human Cytomegalovirus Acquisition, Replication, and Disease","volume":"221","author":"CS Nelson","year":"2020","journal-title":"J Infect Dis"},{"issue":"12","key":"ppat.1009169.ref065","doi-asserted-by":"crossref","first-page":"e1007452","DOI":"10.1371\/journal.ppat.1007452","article-title":"Different functional states of fusion protein gB 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