{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T01:08:35Z","timestamp":1793668115666,"version":"4.5.1"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"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":["R01AI100933"],"award-info":[{"award-number":["R01AI100933"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytomegalovirus is a leading cause of congenital disease, and multiple strains enable congenital CMV (cCMV) from both primary and non-primary infections. Therefore, a cross-strain protective cCMV vaccine is a high priority. Guinea pigs are the only small animal model for cCMV and guinea pig cytomegalovirus (GPCMV) encodes functional homolog proteins, including cell entry gB glycoprotein and non-structural immediate early 1 protein (IE1), which are essential for lytic infection. A gB vaccine antibody response fails to provide horizontal protection against highly cell-associated clinical GPCMV strain TAMYC compared to prototype strain 22122. Previously, a recombinant defective adenovirus (Ad) vaccine encoding IE1, a T cell antigen, provided high-level cCMV protection. In this study, we hypothesized that a combined Ad-based strategy encoding trimeric gB complex and IE1 (AdgB + AdIE1) could improve cross-strain protection against cCMV compared to a gB vaccine (AdgB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A preconception vaccine study was conducted to evaluate the immune response and ability of vaccines to provide cross-strain protection against cCMV. Seronegative female animals were assigned to three vaccine groups: Group 1 (AdgB), Group 2 (AdgB + AdIE1), and Group 3 (no vaccine). Animals were vaccinated following a previously defined protocol, and antibody ELISAs were used to evaluate the gB immune response (AD1, prefusion gB, and wild-type gB). Additionally, an IFN\u03b3-ELISPOT assay was used to evaluate the IE1 T-cell response. During the second trimester, dams were challenged with GPCMV (22122 and TAMYC co-infection), and pregnancy proceeded to term. Viral loads in pup target organs (liver, lung, spleen, brain), blood, and placenta were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Vaccinated dams elicited a higher gB neutralizing antibody response than that of experimentally infected convalescent animals. Antibodies recognized homolog AD1 gB domain as well as prefusion gB with a response surpassing that in GPCMV-infected convalescent animals. Group 2 dams also elicited a T cell response to IE1. Evaluation of viral load in pups demonstrated that the AdgB + AdIE1 vaccine reduced GPCMV transmission to below detectable limits compared to 91.7% in the unvaccinated group. In contrast, AdgB reduced cCMV transmission to 12% in the pups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Complete cross-strain cCMV protection is a significant milestone in this model and is achieved by the inclusion of an antibody response to trimeric gB and T-cell response to IE1. Importantly, gB and IE1 responses can synergize and increase protection against cCMV, unlike prior approaches with gB and pp65 tegument proteins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1649656","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T05:32:05Z","timestamp":1761111125000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Complete cross strain protection against congenital cytomegalovirus infection requires a vaccine encoding key antibody (gB) and T-cell (immediate early 1 protein) viral antigens"],"prefix":"10.3389","volume":"16","author":[{"given":"K. 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