ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1649656
This article is part of the Research TopicInfectious Diseases in Maternal-Fetal Interface: Role of Immune System to Combat this Pathology and Avoid or Minimize a Possible Vertical TransmissionView all 3 articles
Complete cross strain protection against congenital cytomegalovirus infection requires a vaccine encoding key antibody (gB) and T-cell (immediate early 1 protein) viral antigens
Provisionally accepted
- Dept. Microbial Pathogenesis & Immunology, Texas A&M University School of Medicine, Bryan, United States
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Background. 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. 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 fails to provide horizontal protection against highly cell-associated clinical GPCMV strain TAMYC compared to prototype strain 22122. Previously, a recombinant 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 cCMV protection compared to a gB vaccine (AdgB). Methods. A preconception vaccine study evaluated the immune response and 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 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 IFNγ-ELISPOT assay evaluated IE1 T-cell response. During second trimester dams were challenged with GPCMV (22122 and TAMYC co-infection) and pregnancy went to term. Viral loads in pup target organs (liver, lung, spleen, brain) and blood together with placenta were evaluated. Results. Vaccinated dams elicited a higher gB neutralizing antibody response to gB than natural GPCMV experimentally infected convalescent animals. A and antibodies recognized homolog AD1 gB domain as well as prefusion gB with response surpassing that in GPCMV convalescent animal natural immunity. Group 2 dams 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%. Conclusion. 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.
Keywords: Cytomegalovirus, CMV, Congenital CMV, GB, IE1, CMV vaccine, Placenta, guinea pig
Received: 18 Jun 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Choi, Qin, El-Hamdi and McGregor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alistair McGregor, mcgalistair2013@tamu.edu
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