{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:01:51Z","timestamp":1761897711122,"version":"3.37.3"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["#P28102"],"award-info":[{"award-number":["#P28102"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["5P01AI129859"],"award-info":[{"award-number":["5P01AI129859"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Karl Landsteiner Institute for Microbiome Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cytomegalovirus (CMV) genome is highly variable and heterosubtypic immunity should be considered in vaccine development since it can enhance protection in a cross-reactive manner. Here, we developed a protein array to evaluate heterosubtypic immunity to CMV glycoprotein B (gB) in natural infection and vaccination. DNA sequences of four antigenic domains (AD1, AD2, AD4\/5, and AD5) of gB were amplified from six reference and 12 clinical CMV strains, and the most divergent genotypes were determined by phylogenetic analysis. Assigned genotypes were in vitro translated and immobilized on protein array. Then, we tested immune response of variable serum groups (primarily infected patients, reactivated CMV infections and healthy individuals with latent CMV infection, as well gB-vaccinated rabbits) with protein in situ array (PISA). Serum antibodies of all patient cohorts and gB-vaccinated rabbits recognized many genetic variants of ADs on protein array, including but not limited to the subtype of infecting strain. High-grade cross-reactivity was observed. In several patients, we observed none or neglectable immune response to AD1 and AD2, while the same patients showed high antibody response to AD4\/5 and AD5. Among the primary infected patients, AD5 was the predominant AD, in antibody response. The most successful CMV vaccine to date contains gB and demonstrates only 50% efficacy. In this study, we showed that heterosubtypic and cross-reactive immunity to CMV gB is extensive. Therefore, the failure of CMV gB vaccines cannot be explained by a highly, strain-specific immunity. Our observations suggest that other CMV antigens should be addressed in vaccine design.<\/jats:p>","DOI":"10.1093\/cei\/uxac031","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T21:12:12Z","timestamp":1649452332000},"page":"245-254","source":"Crossref","is-referenced-by-count":3,"title":["Heterosubtypic, cross-reactive immunity to human Cytomegalovirus glycoprotein B"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-3793","authenticated-orcid":false,"given":"Ceren","family":"Bilgilier","sequence":"first","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"K\u00fchrer","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Normann","family":"Kilb","sequence":"additional","affiliation":[{"name":"BioCopy GmbH , Emmendingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Hartl","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thais","family":"Topakian","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Theres","family":"Kastner","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Herz","sequence":"additional","affiliation":[{"name":"BioCopy GmbH , Emmendingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cody S","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Brigham and Women\u2019s Hospital , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sallie R","family":"Permar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Weill Cornell Medicine , New York, NY , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"Roth","sequence":"additional","affiliation":[{"name":"BioCopy GmbH , Emmendingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Steininger","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna , Vienna , Austria"},{"name":"Karl-Landsteiner Society Institute of Microbiome Research , Vienna , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"2023081113315986100_CIT0001","doi-asserted-by":"crossref","first-page":"7437","DOI":"10.1016\/j.vaccine.2018.02.089","article-title":"Vaccination against the human cytomegalovirus.","volume":"37","author":"Plotkin","year":"2019","journal-title":"Vaccine"},{"key":"2023081113315986100_CIT0002","doi-asserted-by":"crossref","first-page":"e1005227","DOI":"10.1371\/journal.ppat.1005227","article-title":"Crystal structure of the human cytomegalovirus glycoprotein B.","volume":"11","author":"Burke","year":"2015","journal-title":"PLoS Pathog"},{"key":"2023081113315986100_CIT0003","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.vaccine.2015.11.056","article-title":"Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: a randomized clinical trial.","volume":"34","author":"Bernstein","year":"2016","journal-title":"Vaccine"},{"key":"2023081113315986100_CIT0004","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1056\/NEJMoa0804749","article-title":"Vaccine prevention of maternal cytomegalovirus infection.","volume":"360","author":"Pass","year":"2009","journal-title":"N Engl J Med"},{"key":"2023081113315986100_CIT0005","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":"Nelson","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023081113315986100_CIT0006","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1128\/JVI.02393-14","article-title":"Identification of a neutralizing epitope within antigenic domain 5 of glycoprotein B of human cytomegalovirus.","volume":"89","author":"Wiegers","year":"2015","journal-title":"J Virol"},{"key":"2023081113315986100_CIT0007","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1182\/blood-2003-06-1937","article-title":"Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural 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