{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T17:02:52Z","timestamp":1761238972549,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI098984; R01AI100933; R01AI155561"],"award-info":[{"award-number":["R01AI098984; R01AI100933; R01AI155561"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD090065"],"award-info":[{"award-number":["R01HD090065"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Congenital cytomegalovirus (CMV) is a leading cause of disease in newborns and a vaccine is a high priority. The guinea pig is the only small animal model for congenital CMV but requires guinea pig cytomegalovirus (GPCMV). Previously, a disabled infectious single cycle (DISC) vaccine strategy demonstrated complete protection against congenital GPCMV (22122 strain) and required neutralizing antibodies to various viral glycoprotein complexes. This included gB, essential for all cell types, and the pentamer complex (PC) for infection of non-fibroblast cells. All GPCMV research has utilized prototype strain 22122 limiting the translational impact, as numerous human CMV strains exist allowing re-infection and congenital CMV despite convalescent immunity. A novel GPCMV strain isolate (designated TAMYC) enabled vaccine cross strain protection studies. A GPCMV DISC (PC+) vaccine (22122 strain) induced a comprehensive immune response in animals, but vaccinated animals challenged with the TAMYC strain virus resulted in sustained viremia and the virus spread to target organs (liver, lung and spleen) with a significant viral load in the salivary glands. Protection was better than natural convalescent immunity, but the results fell short of previous DISC vaccine sterilizing immunity against the homologous 22122 virus challenge, despite a similarity in viral glycoprotein sequences between strains. The outcome suggests a limitation of the current DISC vaccine design against heterologous infection.<\/jats:p>","DOI":"10.3390\/v14040760","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T22:23:23Z","timestamp":1649370203000},"page":"760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model"],"prefix":"10.3390","volume":"14","author":[{"given":"K. Yeon","family":"Choi","sequence":"first","affiliation":[{"name":"Department Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-0763","authenticated-orcid":false,"given":"Nadia S.","family":"El-Hamdi","sequence":"additional","affiliation":[{"name":"Department Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alistair","family":"McGregor","sequence":"additional","affiliation":[{"name":"Department Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.spid.2004.09.011","article-title":"Congenital cytomegalovirus infection: Outcome and diagnosis","volume":"16","author":"Ross","year":"2005","journal-title":"Semin. Pediatr. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/01.qco.0000168385.39390.1b","article-title":"Cytomegalovirus","volume":"18","author":"Griffiths","year":"2005","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0022-3476(99)70328-8","article-title":"Newborn hearing screening: Will children with hearing loss caused by congenital cytomegalovirus infection be missed?","volume":"135","author":"Fowler","year":"1999","journal-title":"J. Pediatr."},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jama.289.8.1008","article-title":"Maternal immunity and prevention of congenital cytomegalovirus infection","volume":"289","author":"Fowler","year":"2003","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1084\/jem.20050882","article-title":"Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects","volume":"202","author":"Sylwester","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0065-3527(08)00405-3","article-title":"Rhesus cytomegalovirus a nonhuman primate model for the study of human cytomegalovirus","volume":"72","author":"Yue","year":"2008","journal-title":"Adv. Virus Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1128\/jvi.55.2.402-409.1985","article-title":"The placenta as a site of cytomegalovirus infection in guinea pigs","volume":"55","author":"Griffith","year":"1985","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/infdis\/160.6.929","article-title":"Congenital cytomegalovirus labyrinthitis and sensorineural hearing loss in guinea pigs","volume":"160","author":"Woolf","year":"1989","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3181\/00379727-96-23455","article-title":"Serial propagation of the guinea pig salivary gland virus in tissue culture","volume":"96","author":"Hartley","year":"1957","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Choi, K.Y., El-Hamdi, N.S., and McGregor, A. (2020). Convalescent Immunity to Guinea Pig Cytomegalovirus Induces Limited Cross Strain Protection against Re-Infection but High-Level Protection against Congenital Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21175997"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00268-17","DOI":"10.1128\/CVI.00268-17","article-title":"Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection","volume":"24","author":"Schleiss","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tabata, T., Petitt, M., Fang-Hoover, J., Freed, D.C., Li, F., An, Z., Wang, D., Fu, T.M., and Pereira, L. (2019). Neutralizing Monoclonal Antibodies Reduce Human Cytomegalovirus Infection and Spread in Developing Placentas. Vaccines, 7.","DOI":"10.3390\/vaccines7040135"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.tim.2020.04.003","article-title":"Role of Neutralizing Antibodies in CMV Infection: Implications for New Therapeutic Approaches","volume":"28","author":"Sandonis","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_16","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":"ref_17","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":"ref_18","doi-asserted-by":"crossref","unstructured":"Coleman, S., Hornig, J., Maddux, S., Choi, K.Y., and McGregor, A. (2015). Viral Glycoprotein Complex Formation, Essential Function and Immunogenicity in the Guinea Pig Model for Cytomegalovirus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137942"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Coleman, S., Choi, K.Y., Root, M., and McGregor, A. (2016). A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005755"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.virol.2013.03.008","article-title":"Characterization of the guinea pig CMV gH\/gL\/GP129\/GP131\/GP133 complex in infection and spread","volume":"441","author":"Auerbach","year":"2013","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Choi, K.Y., El-Hamdi, N., and McGregor, A. (2021). Endothelial cell infection by guinea pig cytomegalovirus is a lytic or persistent infection dependent upon tissue origin but requires viral pentamer complex and pp65 tegument protein. J. Virol.","DOI":"10.1128\/jvi.00831-22"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.virol.2017.06.008","article-title":"Cytomegalovirus UL128 homolog mutants that form a pentameric complex produce virus with impaired epithelial and trophoblast cell tropism and altered pathogenicity in the guinea pig","volume":"509","author":"Coleman","year":"2017","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1099\/jgv.0.001394","article-title":"Requirements for guinea pig cytomegalovirus tropism and antibody neutralization on placental amniotic sac cells","volume":"101","author":"Choi","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7902","DOI":"10.1128\/JVI.00283-16","article-title":"A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection","volume":"90","author":"Choi","year":"2016","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1006\/viro.1994.1294","article-title":"Identification of an abundant disulfide-linked complex of glycoproteins in the envelope of guinea pig cytomegalovirus","volume":"201","author":"Britt","year":"1994","journal-title":"Virology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0166-0934(02)00258-6","article-title":"Cloning and expression of the guinea pig cytomegalovirus glycoprotein B (gB) in a recombinant baculovirus: Utility for vaccine studies for the prevention of experimental infection","volume":"108","author":"Schleiss","year":"2003","journal-title":"J. Virol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1016\/j.vaccine.2020.01.063","article-title":"Neutralizing antibodies to gB based CMV vaccine requires full length antigen but reduced virus neutralization on non-fibroblast cells limits vaccine efficacy in the guinea pig model","volume":"38","author":"Choi","year":"2020","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1086\/382751","article-title":"Protection against congenital cytomegalovirus infection and disease in guinea pigs, conferred by a purified recombinant glycoprotein B vaccine","volume":"189","author":"Schleiss","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1016\/j.vaccine.2013.04.078","article-title":"Effects of immunization of pregnant guinea pigs with guinea pig cytomegalovirus glycoprotein B on viral spread in the placenta","volume":"31","author":"Hashimoto","year":"2013","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.vaccine.2016.03.005","article-title":"Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection","volume":"34","author":"Cardin","year":"2016","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1016\/j.vaccine.2015.06.019","article-title":"Comparison of monovalent glycoprotein B with bivalent gB\/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality","volume":"33","author":"Swanson","year":"2015","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.cell.2018.06.028","article-title":"An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor","volume":"174","author":"Marcandalli","year":"2018","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7043","DOI":"10.1073\/pnas.1814850116","article-title":"OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism","volume":"116","author":"Xiaofei","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00781-18","DOI":"10.1128\/mBio.00781-18","article-title":"CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells","volume":"9","author":"Vanarsdall","year":"2018","journal-title":"mBio"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1038\/s41467-019-10587-1","article-title":"CD46 facilitates entry and dissemination of human cytomegalovirus","volume":"10","author":"Stein","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15470","DOI":"10.1073\/pnas.0406821101","article-title":"Cellular integrins function as entry receptors for human cytomegalovirus via a highly conserved disintegrin-like domain","volume":"101","author":"Feire","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wu, Y., Prager, A., Boos, S., Resch, M., Brizic, I., Mach, M., Wildner, S., Scrivano, L., and Adler, B. (2017). Human cytomegalovirus glycoprotein complex gH\/gL\/gO uses PDGFR-alpha as a key for entry. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006281"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e01442-19","DOI":"10.1128\/JVI.01442-19","article-title":"Inclusion of the Viral Pentamer Complex in a Vaccine Design Greatly Improves Protection against Congenital Cytomegalovirus in the Guinea Pig Model","volume":"93","author":"Choi","year":"2019","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.virol.2020.05.012","article-title":"Guinea pig cytomegalovirus trimer complex gH\/gL\/gO uses PDGFRA as universal receptor for cell fusion and entry","volume":"548","author":"Choi","year":"2020","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E4997","DOI":"10.1073\/pnas.1316517110","article-title":"Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine","volume":"110","author":"Freed","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e02033-16","DOI":"10.1128\/JVI.02033-16","article-title":"Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH\/gL\/pUL128-131 Pentameric Complex","volume":"91","author":"Ha","year":"2017","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11884","DOI":"10.1128\/JVI.01701-15","article-title":"Vaccine-Derived Neutralizing Antibodies to the Human Cytomegalovirus gH\/gL Pentamer Potently Block Primary Cytotrophoblast Infection","volume":"89","author":"Chiuppesi","year":"2015","journal-title":"J. Virol."},{"key":"ref_43","first-page":"142","article-title":"Adaptive Cellular Immunity to Human Cytomegalovirus","volume":"Volume II","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9872","DOI":"10.1128\/JVI.78.18.9872-9889.2004","article-title":"Molecular, biological, and in vivo characterization of the guinea pig cytomegalovirus (CMV) homologs of the human CMV matrix proteins pp71 (UL82) and pp65 (UL83)","volume":"78","author":"McGregor","year":"2004","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1086\/511982","article-title":"Preconceptual administration of an alphavirus replicon UL83 (pp65 homolog) vaccine induces humoral and cellular immunity and improves pregnancy outcome in the guinea pig model of congenital cytomegalovirus infection","volume":"195","author":"Schleiss","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e00324-21","DOI":"10.1128\/JVI.00324-21","article-title":"Guinea pig cytomegalovirus protective T cell antigen GP83 is a functional pp65 homolog for innate immune evasion and pentamer dependent virus tropism","volume":"95","author":"Choi","year":"2021","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"362ra145","DOI":"10.1126\/scitranslmed.aaf9387","article-title":"A replication-defective human cytomegalovirus vaccine for prevention of congenital infection","volume":"8","author":"Wang","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"001579","DOI":"10.1099\/jgv.0.001579","article-title":"A trimeric capable gB CMV vaccine provides limited protection against a highly cell associated and epithelial tropic strain of cytomegalovirus in guinea pigs","volume":"102","author":"Choi","year":"2021","journal-title":"J. Gen. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1099\/vir.0.19508-0","article-title":"Antibody responses to rhesus cytomegalovirus glycoprotein B in naturally infected rhesus macaques","volume":"84","author":"Yue","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14118","DOI":"10.1073\/pnas.0804365105","article-title":"HCMV gH\/gL\/UL128-131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptors","volume":"105","author":"Ryckman","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.virol.2010.10.028","article-title":"Guinea pig cytomegalovirus GP84 is a functional homolog of the human cytomegalovirus (HCMV) UL84 gene that can complement for the loss of UL84 in a chimeric HCMV","volume":"410","author":"McGregor","year":"2011","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9680","DOI":"10.1128\/JVI.01167-13","article-title":"Comparative analysis of gO isoforms reveals that strains of human cytomegalovirus differ in the ratio of gH\/gL\/gO and gH\/gL\/UL128-131 in the virion envelope","volume":"87","author":"Zhou","year":"2013","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00606-18","DOI":"10.1128\/JVI.00606-18","article-title":"Expression Levels of Glycoprotein O (gO) Vary between Strains of Human Cytomegalovirus, Influencing the Assembly of gH\/gL Complexes and Virion Infectivity","volume":"92","author":"Zhang","year":"2018","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e02051-19","DOI":"10.1128\/JVI.02051-19","article-title":"Polymorphisms in Human Cytomegalovirus Glycoprotein O (gO) Exert Epistatic Influences on Cell-Free and Cell-to-Cell Spread and Antibody Neutralization on gH Epitopes","volume":"94","author":"Day","year":"2020","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9988","DOI":"10.1073\/pnas.0604157103","article-title":"The guinea pig as a transmission model for human influenza viruses","volume":"103","author":"Lowen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1128\/JVI.00160-08","article-title":"Laboratory strains of murine cytomegalovirus are genetically similar to but phenotypically distinct from wild strains of virus","volume":"82","author":"Smith","year":"2008","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wagner, F.M., Brizic, I., Prager, A., Trsan, T., Arapovic, M., Lemmermann, N.A., Podlech, J., Reddehase, M.J., Lemnitzer, F., and Bosse, J.B. (2013). The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH\/gL\/MCK-2 complex. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003493"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1093\/infdis\/jiz484","article-title":"Animal Models of Congenital Cytomegalovirus Transmission: Implications for Vaccine Development","volume":"221","author":"Roark","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Taher, H., Mahyari, E., Kreklywich, C., Uebelhoer, L.S., McArdle, M.R., Mostrom, M.J., Bhusari, A., Nekorchuk, M., E, X., and Whitmer, T. (2020). In vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008666"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e94002","DOI":"10.1172\/jci.insight.94002","article-title":"Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys","volume":"2","author":"Nelson","year":"2017","journal-title":"JCI Insight"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1056\/NEJMoa1310214","article-title":"A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus","volume":"370","author":"Revello","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJMoa1913569","article-title":"A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection","volume":"385","author":"Hughes","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.coviro.2017.08.005","article-title":"Rhesus monkeys for a nonhuman primate model of cytomegalovirus infections","volume":"25","author":"Itell","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.vaccine.2018.08.043","article-title":"Comparison of vaccination with rhesus CMV (RhCMV) soluble gB with a RhCMV replication-defective virus deleted for MHC class I immune evasion genes in a RhCMV challenge model","volume":"37","author":"Valencia","year":"2019","journal-title":"Vaccine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.virol.2017.01.023","article-title":"The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting","volume":"504","author":"Hornig","year":"2017","journal-title":"Virology"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Choi, K.Y., and McGregor, A. (2021). A Fully Protective Congenital CMV Vaccine Requires Neutralizing Antibodies to Viral Pentamer and gB Glycoprotein Complexes but a pp65 T-Cell Response Is Not Necessary. Viruses, 13.","DOI":"10.3390\/v13081467"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1016\/j.vaccine.2008.07.103","article-title":"A heterologous DNA prime\/protein boost immunization strategy for rhesus cytomegalovirus","volume":"26","author":"Abel","year":"2008","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1099\/jgv.0.000882","article-title":"The pentameric complex of human Cytomegalovirus: Cell tropism, virus dissemination, immune response and vaccine development","volume":"98","author":"Gerna","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.2217\/fvl.13.107","article-title":"An Attenuated CMV Vaccine with a Deletion in Tegument Protein GP83 (pp65 Homolog) Protects against Placental Infection and Improves Pregnancy Outcome in a Guinea Pig Challenge Model","volume":"8","author":"Schleiss","year":"2013","journal-title":"Future Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e00747-19","DOI":"10.1128\/JVI.00747-19","article-title":"A Replication-Defective Human Cytomegalovirus Vaccine Elicits Humoral Immune Responses Analogous to Those with Natural Infection","volume":"93","author":"Liu","year":"2019","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e0065721","DOI":"10.1128\/JVI.00657-21","article-title":"A Novel Strain-Specific Neutralizing Epitope on Glycoprotein H of Human Cytomegalovirus","volume":"95","author":"Thomas","year":"2021","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1128\/JVI.01669-12","article-title":"A vaccine based on the rhesus cytomegalovirus UL128 complex induces broadly neutralizing antibodies in rhesus macaques","volume":"87","author":"Wussow","year":"2013","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e02422-20","DOI":"10.1128\/AAC.02422-20","article-title":"Potent Bispecific Neutralizing Antibody Targeting Glycoprotein B and the gH\/gL\/pUL128\/130\/131 Complex of Human Cytomegalovirus","volume":"65","author":"Su","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1185350","article-title":"Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus","volume":"328","author":"Hansen","year":"2010","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1128\/JVI.00883-10","article-title":"Vaccine-induced control of viral shedding following rhesus cytomegalovirus challenge in rhesus macaques","volume":"85","author":"Abel","year":"2011","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e01774-17","DOI":"10.1128\/JVI.01774-17","article-title":"Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens Type I Interferon Production by Inactivating the DNA Sensor cGAS without Affecting STING","volume":"92","author":"Biolatti","year":"2018","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/760\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:03Z","timestamp":1760136543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":76,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["v14040760"],"URL":"https:\/\/doi.org\/10.3390\/v14040760","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,4,6]]}}}