{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:41:26Z","timestamp":1768524086416,"version":"3.49.0"},"posted":{"date-parts":[[2025,6,20]]},"group-title":"Immunology","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01AI100933"],"award-info":[{"award-number":["R01AI100933"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01AI098984"],"award-info":[{"award-number":["R01AI098984"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NICHD","award":["R01HD090065"],"award-info":[{"award-number":["R01HD090065"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,20]]},"abstract":"<jats:title>\n                  <jats:bold>Abstract<\/jats:bold>\n                <\/jats:title>\n                <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 infection. A cross-strain protective cCMV vaccine is a high priority. The guinea pig is 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), 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 evaluated the immune response and ability of vaccines to provide cross-strain protection against cCMV. Seronegative female animals were assigned into three vaccine groups: Group 1 (AdgB); Group 2 (AdgB+AdIE1); Group 3 (no vaccine). Animals were vaccinated following a previously defined protocol and antibody ELISAs were used to evaluate gB immune response (AD1, prefusion gB and wild type gB). Additionally, an IFN\u03b3-ELISPOT assay evaluated IE1 T-cell response. During second trimester dams were challenged with GPCMV (22122 and TAMYC) and pregnancy went to term where viral loads in pup target organs and placentas were evaluated.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Vaccinated dams elicited a higher neutralizing antibody response to gB than natural convalescent immunity and antibodies recognized homolog AD1 gB domain as well as prefusion gB with response surpassing natural immunity. Group 2 animals additionally elicited a T-cell response to IE1. Evaluation of viral load in pups demonstrated that AdgB+AdIE1 vaccine reduced GPCMV transmission to below detectable limits compared to 91.7% in unvaccinated group. In contrast, AdgB reduced cCMV transmission to 12% in 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 achieved by 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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.18.660432","type":"posted-content","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:19Z","timestamp":1750464019000},"source":"Crossref","is-referenced-by-count":0,"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":"10.64898","author":[{"given":"K. 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