{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:51Z","timestamp":1787030031248,"version":"build-2736575974"},"reference-count":129,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Herpesviruses have been isolated from a wide range of hosts including humans\u2014for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein\u2013Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required.<\/jats:p>","DOI":"10.3390\/vaccines8010035","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T03:04:43Z","timestamp":1579575883000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cytomegalovirus and Epstein\u2013Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-5191","authenticated-orcid":false,"given":"Peter A. C.","family":"Maple","sequence":"first","affiliation":[{"name":"Clinical Neurology Research Group, Division of Clinical Neuroscience, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"ref_1","unstructured":"(2019, December 20). Virus Taxonomy: The Classification and Nomenclature of Viruses the Online (10th) Report of the ICTV. Available online: http:\/\/talk.ictvonline.org\/ictv-reports\/ictv_online_report\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.3389\/fmicb.2019.02297","article-title":"Human NK cells and herpesviruses: Mechanisms of recognition, response and adaptation","volume":"10","author":"Chiesa","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1128\/mr.53.3.318-332.1989","article-title":"Human herpesviruses: A consideration of the latent state","volume":"53","author":"Stevens","year":"1989","journal-title":"Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e02105-17","DOI":"10.1128\/JVI.02105-17","article-title":"Herpesvirus evasion of natural killer cells","volume":"92","author":"Romero","year":"2018","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/eji.201646762","article-title":"CMV and natural killer cells: Shaping the response to vaccination","volume":"48","author":"Goodier","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wilski, N.A., and Snyder, C.M. (2019). From vaccine vector to oncomodulation: Understanding the complex interplay between CMV and cancer. Vaccines, 7.","DOI":"10.3390\/vaccines7030062"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fonc.2019.00104","article-title":"Progress in EBV vaccines","volume":"9","author":"Mautner","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1080\/14760584.2017.1394843","article-title":"Varicella and herpes zoster vaccine development: Lessons learned","volume":"16","author":"Forbes","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1086\/379711","article-title":"Cytomegalovirus infection in immunocompetent patients","volume":"37","author":"Wreghitt","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jiac.2019.01.012","article-title":"Clinical differentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan","volume":"25","author":"Ishii","year":"2019","journal-title":"J. Infect. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/infdis\/jiv148","article-title":"The sordid affair between human herpesvirus and HIV","volume":"212","author":"Gianella","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1034\/j.1399-3062.1999.010307.x","article-title":"Prevention and treatment of cytomegalovirus infection in organ transplant recipients","volume":"1","author":"Kusne","year":"1999","journal-title":"Transpl. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1001\/jama.2008.697","article-title":"Cytomegalovirus reactivation in critically ill immunocompetent patients","volume":"300","author":"Limaye","year":"2008","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1542\/peds.2014-1173","article-title":"Hearing loss and congenital CMV infection: A systematic review","volume":"134","author":"Goderis","year":"2014","journal-title":"Pediatrics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.12688\/f1000research.12517.1","article-title":"Maternal and fetal cytomegalovirus infection: Diagnosis, management, and prevention","volume":"7","author":"Pass","year":"2018","journal-title":"F1000Research"},{"key":"ref_16","first-page":"16507","article-title":"Screening for cytomegalovirus infection in pregnancy","volume":"367","author":"Kilby","year":"2019","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/CMR.00062-12","article-title":"The \u201csilent\u201d global burden of congenital cytomegalovirus","volume":"26","author":"Manicklal","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1128\/CMR.2.2.204","article-title":"Acquisition of cytomegalovirus infection: An update","volume":"2","author":"Forbes","year":"1989","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1160\/TH09-04-0213","article-title":"Endothelial cells in human cytomegalovirus infection: One host cell out of many or a crucial target for virus spread?","volume":"102","author":"Adler","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jcv.2007.11.014","article-title":"Human cytomegalovirus: Latency and reactivation in the myeloid lineage","volume":"41","author":"Sinclair","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.virusres.2010.10.031","article-title":"Human cytomegalovirus immunity and immune evasion","volume":"157","author":"Jackson","year":"2011","journal-title":"Virus Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1182\/blood.V88.12.4526.bloodjournal88124526","article-title":"Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells","volume":"88","author":"Sindre","year":"1996","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1083-8791(03)00287-8","article-title":"Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, challenges, and future strategies","volume":"9","author":"Boeckh","year":"2003","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S2055-6640(20)30456-8","article-title":"Human cytomegalovirus (CMV) in Africa: A neglected but important pathogen","volume":"2","author":"Bates","year":"2016","journal-title":"J. Virus Erad."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/cid\/cit083","article-title":"Seropositivity and higher immunoglobulin G antibody levels against cytomegalovirus are associated with mortality in the population-based European prospective investigation of cancer\u2013Norfolk cohort","volume":"56","author":"Langenberg","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1017\/S0950268808001258","article-title":"The burden of infection with cytomegalovirus in England and Wales: How many women are infected in pregnancy?","volume":"137","author":"Vyse","year":"2009","journal-title":"Epidemiol. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pembrey, L., Raynor, P., Griffiths, P., Chaytor, S., Wright, J., and Hall, A.J. (2013). Seroprevalence of cytomegalovirus, Epstein Barr virus and varicella zoster virus among pregnant women in Bradford: A cohort study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081881"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection","volume":"17","author":"Kenneson","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijid.2013.12.010","article-title":"Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries","volume":"22","author":"Lanzieri","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jpeds.2015.11.014","article-title":"Determinants of ethnic differences in cytomegalovirus, Epstein-Barr virus, and herpes simplex virus type 1 seroprevalence in childhood","volume":"170","author":"Jansen","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fowler, K.B., Ross, S.A., Shimamura, M., Ahmed, A., Palmer, A.L., Michaels, M.G., Bernstein, D.I., S\u00e1nchez, P.J., Feja, K.N., and Stewart, A. (2018). Racial and ethnic differences in the prevalence of congenital cytomegalovirus infection. J. Pediatr.","DOI":"10.1016\/j.jpeds.2018.04.043"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1136\/adc.83.5.377","article-title":"Neonatal screening for hearing impairment","volume":"83","author":"Kennedy","year":"2000","journal-title":"Arch. Dis. Child."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Korver, A.M., Smith, R.J., van Camp, G., Schleiss, M.R., Bitner-Glindzicz, M.A., Lustig, L.R., Usami, S.I., and Boudewyns, A.N. (2018). Congenital hearing loss. Nat. Rev. Dis. Primers.","DOI":"10.1038\/nrdp.2016.94"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jcv.2011.07.005","article-title":"Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age","volume":"52","author":"Enders","year":"2011","journal-title":"J. Clin. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Coppola, T., Mangold, J.F., Cantrell, S., and Permar, S.R. (2019). Impact of maternal immunity on congenital cytomegalovirus birth prevalence and infant outcomes: A systematic review. Vaccines, 7.","DOI":"10.3390\/vaccines7040129"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jcv.2007.09.004","article-title":"Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: A quantitative assessment","volume":"41","author":"Grosse","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jpeds.2016.01.024","article-title":"Hearing in children with congenital cytomegalovirus infection: Results of a longitudinal study","volume":"172","author":"Goderis","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Colugnati, F.A., Staras, S.A., Dollard, S.C., and Cannon, M.J. (2007). Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BMC Infect. Dis., 7.","DOI":"10.1186\/1471-2334-7-71"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1093\/cid\/ciq085","article-title":"Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection","volume":"52","author":"Wang","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1128\/JCM.36.12.3540-3544.1998","article-title":"Prenatal diagnosis of congenital cytomegalovirus infection","volume":"36","author":"Lazzarotto","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1128\/CVI.05228-11","article-title":"National prevalence estimates for cytomegalovirus IgM and IgG avidity and association between high IgM avidity titer and low IgG avidity","volume":"18","author":"Dollard","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1128\/CVI.00487-14","article-title":"Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy","volume":"21","author":"Prince","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1016\/S1473-3099(17)30143-3","article-title":"Congenital cytomegalovirus infection in pregnancy and the neonate: Consensus recommendations for prevention, diagnosis, and therapy","volume":"17","author":"Rawlinson","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.1469-0691.2011.03564.x","article-title":"Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy","volume":"17","author":"Lazzarotto","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_45","first-page":"881","article-title":"Prenatal diagnosis of congenital cytomegalovirus infection: Prospective study of 237 pregnancies at risk","volume":"95","author":"Liesnard","year":"2000","journal-title":"Obstet. Gynecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S1386-6532(00)00184-0","article-title":"Congenital HCMV infection: A collaborative and comparative study of virus detection in amniotic fluid by culture and by PCR","volume":"21","author":"Gouarin","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/pd.1970131103","article-title":"Prenatal diagnosis of congenital cytomegalovirus infection: False-negative amniocentesis at 20 weeks\u2019 gestation","volume":"13","author":"Catanzarite","year":"1993","journal-title":"Prenat. Diagn."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/pd.59","article-title":"Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome","volume":"21","author":"Enders","year":"2001","journal-title":"Prenat. Diagn."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1093\/infdis\/jiy057","article-title":"Contribution of breastfeeding to false-positive saliva polymerase chain reaction for newborn congenital cytomegalovirus screening","volume":"217","author":"Ross","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/ajo.12408","article-title":"Congenital cytomegalovirus infection in pregnancy: A review of prevalence, clinical features, diagnosis and prevention","volume":"56","author":"Naing","year":"2016","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1056\/NEJMoa1006561","article-title":"Saliva polymerase-chain reaction assay for cytomegalovirus screening in newborns","volume":"364","author":"Boppana","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1097\/INF.0000000000000609","article-title":"Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection","volume":"34","author":"Pinninti","year":"2015","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1590\/0037-8682-0200-2014","article-title":"The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increases inclusion and detection rates","volume":"48","author":"Cardoso","year":"2015","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"F519","DOI":"10.1136\/archdischild-2016-311859","article-title":"Contribution of targeted saliva screening for congenital CMV-related hearing loss in newborns who fail hearing screening","volume":"102","author":"Lubin","year":"2017","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lu, C.Y., Tsao, P.N., Ke, Y.Y., Lin, Y.H., Lin, Y.H., Hung, C.C., Su, Y.N., Hsu, W.C., Hsieh, W.S., and Huang, L.M. (2018). Concurrent hearing, genetic, and cytomegalovirus screening in newborns, Taiwan. J. Pediatr.","DOI":"10.1016\/j.jpeds.2018.02.064"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hilditch, C., Liersch, B., Spurrier, N., Callender, E.J., Cooper, C., and Keir, A.K. (2018). Does screening for congenital cytomegalovirus at birth improve longer term hearing outcomes?. Arch. Dis. Child.","DOI":"10.1136\/archdischild-2017-314404"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ross, S., Long, S.S., and Kimberlin, D.W. (2018). Closer to universal newborn screening for congenital cytomegalovirus infection but far away from antiviral therapy in all infected infants. J. Pediatr.","DOI":"10.1016\/j.jpeds.2018.03.062"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jcv.2014.04.024","article-title":"Universal neonatal cytomegalovirus screening using saliva\u2013report of clinical experience","volume":"60","author":"Barkai","year":"2014","journal-title":"J. Clin. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.earlhumdev.2011.08.021","article-title":"Evidence based management guidelines for the detection and treatment of congenital CMV","volume":"87","author":"Kadambari","year":"2011","journal-title":"Early Hum. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0022-3476(03)00192-6","article-title":"Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: A randomized, controlled trial","volume":"143","author":"Kimberlin","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1093\/jac\/dkp083","article-title":"Treatment of congenital cytomegalovirus infection: Implications for future therapeutic strategies","volume":"63","author":"Nassetta","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1056\/NEJMoa1404599","article-title":"Valganciclovir for symptomatic congenital cytomegalovirus disease","volume":"372","author":"Kimberlin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00431-010-1176-9","article-title":"Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir","volume":"169","author":"Amir","year":"2010","journal-title":"Eur. J. Pediatr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jcv.2012.06.001","article-title":"Treatment of symptomatic congenital cytomegalovirus infection beyond the neonatal period","volume":"55","author":"Reyes","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Pasternak, Y., Ziv, L., Attias, J., Amir, J., and Bilavsky, E. (2018). Valganciclovir is beneficial in children with congenital cytomegalovirus and isolated hearing loss. J. Pediatr.","DOI":"10.1016\/j.jpeds.2018.02.028"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1097\/INF.0000000000001763","article-title":"Congenital cytomegalovirus: A European expert consensus statement on diagnosis and management","volume":"36","author":"Luck","year":"2017","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/MOP.0000000000000305","article-title":"Advances in the prevention and treatment of congenital cytomegalovirus infection","volume":"28","author":"James","year":"2016","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13052-017-0358-8","article-title":"Congenital cytomegalovirus infection: Advances and challenges in diagnosis, prevention and treatment","volume":"43","author":"Marsico","year":"2017","journal-title":"Ital. J. Pediatr."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Morillo-Gutierrez, B., Waugh, S., Pickering, A., Flood, T., and Emonts, M. (2017). Emerging (val) ganciclovir resistance during treatment of congenital CMV infection: A case report and review of the literature. BMC Pediatr., 17.","DOI":"10.1186\/s12887-017-0933-6"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s11357-017-9986-6","article-title":"CMV immune evasion and manipulation of the immune system with aging","volume":"39","author":"Jackson","year":"2017","journal-title":"GeroScience"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.4049\/jimmunol.180.7.4965","article-title":"Differential initiation of innate immune responses induced by human cytomegalovirus entry into fibroblast cells","volume":"180","author":"Juckem","year":"2008","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Manandhar, T., H\u00f2, G.T., Pump, W.C., Blasczyk, T., and Bade-Doeding, C. (2019). Battle between host immune cellular responses and HCMV immune evasion. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153626"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.humimm.2004.02.014","article-title":"CD8+ T-cell immunity to cytomegalovirus","volume":"65","author":"Moss","year":"2004","journal-title":"Hum. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bootz, A., Karbach, A., Spindler, J., Kropff, B., Reuter, N., Sticht, H., Winkler, T.H., Britt, W.J., and Mach, M. (2017). Protective capacity of neutralizing and non-neutralizing antibodies against glycoprotein B of cytomegalovirus. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006601"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/infdis\/jiz141","article-title":"Phase 1 clinical trial of a conditionally replication-defective human cytomegalovirus (CMV) vaccine in CMV-seronegative subjects","volume":"220","author":"Adler","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_76","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":"ref_77","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.vaccine.2009.09.135","article-title":"Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers","volume":"28","author":"Bernstein","year":"2010","journal-title":"Vaccine"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1093\/infdis\/jiw365","article-title":"A Phase 1 study of 4 live, recombinant human cytomegalovirus Towne\/Toledo chimera vaccines in cytomegalovirus-seronegative men","volume":"214","author":"Adler","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1182\/blood-2016-07-729756","article-title":"MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults","volume":"129","author":"Longmate","year":"2017","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1086\/588385","article-title":"Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects","volume":"197","author":"Wloch","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.micinf.2017.12.010","article-title":"Immune responses to congenital cytomegalovirus infection","volume":"20","author":"Hirsl","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.coviro.2017.02.003","article-title":"Development of a vaccine against cytomegalovirus infection and disease","volume":"23","author":"Luisi","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_83","first-page":"1","article-title":"Human cytomegalovirus (HCMV) infection\/re-infection: Development of a protective HCMV vaccine","volume":"42","author":"Gerna","year":"2019","journal-title":"New Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S2055-6640(20)30872-4","article-title":"Cytomegalovirus vaccines under clinical development","volume":"2","author":"Schleiss","year":"2016","journal-title":"J. Virus Erad."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6980","DOI":"10.1016\/j.vaccine.2012.09.056","article-title":"The next generation recombinant human cytomegalovirus vaccine candidates-beyond gB","volume":"30","author":"Lilja","year":"2012","journal-title":"Vaccine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7328","DOI":"10.1016\/j.vaccine.2015.10.078","article-title":"A cytomegalovirus DNA vaccine induces antibodies that block viral entry into fibroblasts and epithelial cells","volume":"33","author":"McVoy","year":"2015","journal-title":"Vaccine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1128\/CVI.00662-13","article-title":"Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B antigen induces antibodies with potent and broad neutralizing activity","volume":"21","author":"Kirchmeier","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1080\/21645515.2016.1164376","article-title":"Preclinical evaluations of peptide-conjugate vaccines targeting the antigenic domain-2 of glycoprotein B of human cytomegalovirus","volume":"12","author":"Finnefrock","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ebiom.2019.11.005","article-title":"Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation","volume":"50","author":"Baraniak","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/j.vaccine.2018.01.042","article-title":"Cost-effectiveness of vaccination against cytomegalovirus (CMV) in adolescent girls to prevent infections in pregnant women living in France","volume":"36","author":"Launay","year":"2018","journal-title":"Vaccine"},{"key":"ref_91","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":"ref_92","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0140-6736(64)91524-7","article-title":"Virus particles in cultured lymphoblasts from Burkitt\u2019s lymphoma","volume":"1","author":"Epstein","year":"1964","journal-title":"Lancet"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nrc1452","article-title":"Epstein-Barr virus: 40 years on","volume":"4","author":"Young","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3389\/fonc.2019.00713","article-title":"The global landscape of EBV-associated tumours","volume":"9","author":"Rickinson","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.msard.2017.06.002","article-title":"EBV and MS: Major cause, minor contribution or red-herring?","volume":"16","author":"Burnard","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri3871","article-title":"Immunopathology of multiple sclerosis","volume":"15","author":"Dendrou","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1016\/S0140-6736(16)30959-X","article-title":"Diagnosis of multiple sclerosis: Progress and challenges","volume":"389","author":"Brownlee","year":"2017","journal-title":"Lancet"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S0140-6736(16)31320-4","article-title":"Progressive multiple sclerosis: Prospects for disease therapy, repair, and restoration of function","volume":"389","author":"Ontaneda","year":"2017","journal-title":"Lancet"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fneur.2017.00234","article-title":"Primary progressive multiple sclerosis: Putting together the puzzle","volume":"8","author":"Abdelhak","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1136\/jnnp-2013-305450","article-title":"Incidence and prevalence of multiple sclerosis in the UK 1990\u20132010: A descriptive study in the General Practice Research Database","volume":"85","author":"Mackenzie","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1212\/WNL.0000000000000768","article-title":"Atlas of multiple sclerosis 2013: A growing global problem with widespread inequity","volume":"83","author":"Browne","year":"2014","journal-title":"Neurology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"101459","DOI":"10.1016\/j.msard.2019.101459","article-title":"Consensus recommendations for the diagnosis and treatment of multiple sclerosis: 2019 revisions to the MENACTRIMS guidelines","volume":"37","author":"Yamout","year":"2019","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_103","first-page":"527","article-title":"Progressive multiple sclerosis: From pathogenic mechanisms to treatment","volume":"140","author":"Correale","year":"2017","journal-title":"Brain"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/S1474-4422(08)70042-5","article-title":"Environmental factors and multiple sclerosis","volume":"7","author":"Ebers","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S1474-4422(03)00663-X","article-title":"Genetics of multiple sclerosis","volume":"3","author":"Dyment","year":"2004","journal-title":"Lancet Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Almohmeed, Y.H., Avenell, A., Aucott, L., and Vickers, M.A. (2013). Systematic review and meta-analysis of the sero-epidemiological association between Epstein Barr virus and multiple sclerosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061110"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jns.2009.03.028","article-title":"Epstein-Barr virus and multiple sclerosis","volume":"286","author":"Pohl","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.msard.2017.02.019","article-title":"Infectious mononucleosis and multiple sclerosis-updated review on associated risk","volume":"14","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Maple, P.A.C., Tanasescu, R., Gran, B., and Constantinescu, C.S. (2019). A different response to Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in UK people with multiple sclerosis (PwMS) compared to controls. J. Infect.","DOI":"10.1016\/j.jinf.2019.10.017"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S1474-4422(07)70196-5","article-title":"Clinical features and viral serologies in children with multiple sclerosis: A multinational observational study","volume":"6","author":"Bamwell","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1212\/WNL.0b013e3181aa29fe","article-title":"Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI","volume":"73","author":"Farrell","year":"2009","journal-title":"Neurology"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Bar-Or, A., Pender, M.P., Khanna, R., Steinman, L., Hartung, H.P., Maniar, T., Croze, E., Aftab, B.T., Giovannoni, G., and Joshi, M.J. (2019). Epstein-Barr virus in multiple sclerosis: Theory and emerging immunotherapies. Trends Mol. Med.","DOI":"10.1016\/j.molmed.2019.11.003"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e00980-19","DOI":"10.1128\/JVI.00980-19","article-title":"Epstein-Barr virus-specific CD8 T cells selectively infiltrate the brain in multiple sclerosis and interact locally with virus-infected cells: Clue for a virus-driven immunopathological mechanism","volume":"93","author":"Serafini","year":"2019","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"124714","DOI":"10.1172\/jci.insight.124714","article-title":"Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis","volume":"3","author":"Pender","year":"2018","journal-title":"JCI Insight"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1136\/jclinpath-2019-205822","article-title":"Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors","volume":"72","author":"Kerr","year":"2019","journal-title":"J. Clin. Pathol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.msard.2018.02.029","article-title":"Could antivirals be treating EBV in MS? A case report","volume":"22","author":"Drosu","year":"2018","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1038\/cti.2014.27","article-title":"Epstein-barr virus vaccines","volume":"4","author":"Cohen","year":"2015","journal-title":"Clin. Transl. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Balfour, H.H., Schmeling, D.O., and Grimm-Geris, J.M. (2019). The promise of a prophylactic Epstein-Barr virus vaccine. Pediatr. Res.","DOI":"10.1038\/s41390-019-0591-5"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/978-981-10-7230-7_22","article-title":"Vaccine development for Epstein-Barr virus","volume":"1045","author":"Cohen","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_120","first-page":"171","article-title":"First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen","volume":"84","author":"Gu","year":"1995","journal-title":"Dev. Biol. Stand."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1086\/523813","article-title":"Recombinant gp350 vaccine for infectious mononucleosis: A Phase 2 randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults","volume":"196","author":"Sokal","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"13105","DOI":"10.1128\/JVI.05598-11","article-title":"A virus-like particle-based Epstein-Barr virus vaccine","volume":"85","author":"Ruiss","year":"2011","journal-title":"J. Virol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1128\/JVI.01409-07","article-title":"Phase 1 trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis","volume":"82","author":"Elliott","year":"2008","journal-title":"J. Virol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"373","DOI":"10.4103\/1673-5374.245462","article-title":"The role of Epstein-Barr virus in multiple sclerosis: From molecular pathophysiology to in vivo imaging","volume":"14","author":"Guan","year":"2019","journal-title":"Neural. Regen. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1016\/j.vaccine.2014.03.057","article-title":"Progress on pursuit of human cytomegalovirus vaccines for prevention of congenital infection and disease","volume":"32","author":"Fu","year":"2014","journal-title":"Vaccine"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6273","DOI":"10.1073\/pnas.1800224115","article-title":"Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies","volume":"115","author":"Baraniak","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e1514921","DOI":"10.1080\/2162402X.2018.1514921","article-title":"The role of CMV in glioblastoma and implications for immunotherapeutic strategies","volume":"8","author":"Rahman","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12985-018-0937-3","article-title":"Human cytomegalovirus infection and coronary heart disease: A systematic review","volume":"15","author":"Du","year":"2018","journal-title":"Virol. J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.autrev.2011.08.005","article-title":"Autoimmune disease: A role for new anti-viral therapies?","volume":"11","author":"Dreyfus","year":"2011","journal-title":"Autoimmun. Rev."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/35\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:44:11Z","timestamp":1760363051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/35"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":129,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["vaccines8010035"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8010035","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,20]]}}}