{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T16:52:41Z","timestamp":1775926361611,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD079918"],"award-info":[{"award-number":["HD079918"]}],"id":[{"id":"10.13039\/100000071","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":["HD098866"],"award-info":[{"award-number":["HD098866"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The development of a vaccine against congenital human cytomegalovirus (HCMV) infection is a major priority. The pentameric complex (PC) of virion envelope proteins gH, gL, UL128, UL130, and UL131A is a key vaccine target. To determine the importance of immunity to the homologous PC encoded by guinea pig cytomegalovirus (GPCMV) in preventing congenital CMV, PC-intact and PC-deficient live-attenuated vaccines were generated and directly compared for immunogenicity and efficacy against vertical transmission in a vertical transmission model. A virulent PC-intact GPCMV (PC\/intact) was modified by galK mutagenesis either to abrogate PC expression (PC\/null; containing a frame-shift mutation in GP129, homolog of UL128) or to delete genes encoding three MHC Class I homologs and a protein kinase R (PKR) evasin while retaining the PC (3DX\/\u0394145). Attenuated vaccines were compared to sham immunization in a two-dose preconception subcutaneous inoculation regimen in GPCMV seronegative Hartley guinea pigs. Vaccines induced transient, low-grade viremia in 5\/12 PC\/intact-, 2\/12 PC\/null-, and 1\/11 3DX\/\u0394145-vaccinated animals. Upon completion of the two-dose vaccine series, ELISA titers for the PC\/intact group (geometic mean titer (GMT) 13,669) were not significantly different from PC\/null (GMT 8127) but were significantly higher than for the 3DX\/\u0394145 group (GMT 6185; p &lt; 0.01). Dams were challenged with salivary gland-adapted GPCMV in the second trimester. All vaccines conferred protection against maternal viremia. Newborn weights were significantly lower in sham-immunized controls (84.5 \u00b1 2.4 g) compared to PC\/intact (96 \u00b1 2.3 g), PC\/null (97.6 \u00b1 1.9 g), or 3DX\/\u0394145 (93 \u00b1 1.7) pups (p &lt; 0.01). Pup mortality in sham-immunized controls was 29\/40 (73%) and decreased to 1\/44 (2.3%), 2\/46 (4.3%), or 4\/40 (10%) in PC\/intact, PC\/null, or 3DX\/\u0394145 groups, respectively (all p &lt; 0.001 compared to control). Congenital GPCMV transmission occurred in 5\/44 (11%), 16\/46 (35%), or 29\/38 (76%) of pups in PC\/intact, PC\/null, or 3DX\/\u0394145 groups, versus 36\/40 (90%) in controls. For infected pups, viral loads were lower in pups born to vaccinated dams compared to controls. Sequence analysis demonstrated that infected pups in the vaccine groups had salivary gland-adapted GPCMV and not vaccine strain-specific sequences, indicating that congenital transmission was due to the challenge virus and not vaccine virus. We conclude that inclusion of the PC in a live, attenuated preconception vaccine improves immunogenicity and reduces vertical transmission, but PC-null vaccines are equal to PC-intact vaccines in reducing maternal viremia and protecting against GPCMV-related pup mortality.<\/jats:p>","DOI":"10.3390\/v13122370","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:12:56Z","timestamp":1638328376000},"page":"2370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-9433","authenticated-orcid":false,"given":"Mark R.","family":"Schleiss","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-7792","authenticated-orcid":false,"given":"Claudia","family":"Fern\u00e1ndez-Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelmary","family":"Hernandez-Alvarado","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian Ben","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam P.","family":"Geballe","sequence":"additional","affiliation":[{"name":"Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-7870","authenticated-orcid":false,"given":"Michael A.","family":"McVoy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.4437","article-title":"The pathogenesis of human cytomegalovirus","volume":"235","author":"Griffiths","year":"2014","journal-title":"J. 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