Cross-herpesvirus immunity of the cytomegalovirus gB/MF59 vaccine response
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Vaccination against human cytomegalovirus (HCMV) to protect transplant recipients and prevent congenital infection remains highest priority. Follow-up analyses of a vaccine directed against the fusion protein glycoprotein B (gB/MF59) identified a vaccine-specific response (AD-6) that correlated with protection. Subsequently, it was demonstrated that AD-6 antibodies are anti-viral by preventing cell-associated spread. Here we now demonstrate AD-6 antibodies limit HCMV reactivation – an event critical for pathogenesis via hematogenic spread in vivo. To better understand the AD-6 immunogen, we use structural homology to identify putative AD-6 regions in related herpesviruses and show, despite limited sequence similarity, they share key physico-chemical properties. Of note was that AD-6 mapped to a region under high molecular frustration within gB – arguing AD-6 antibodies inhibit gB function by targeting activity dependent on conserved conformational changes. Consistent with structural conformation being crucial, we observe that both rabbit and human HCMV AD-6 antibodies recognise other herpesvirus AD-6s and that AD-6 antibodies are potently antiviral against HSV-1. Thus, a combinatorial in silico, biochemical and immunological approach reveals conformational epitopes within AD-6 are critical components of the gB/MF59 vaccine, represent crucial conserved elements of AD-6 in gB structure and function which makes it an attractive target of multiple herpesviruses.
Date Issued
2025-12-05
Date Acceptance
2025-11-06
Citation
npj Vaccines, 2025, 10
ISSN
2059-0105
Publisher
Nature Portfolio
Journal / Book Title
npj Vaccines
Volume
10
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41350277
PII: 10.1038/s41541-025-01315-6
Publication Status
Published
Coverage Spatial
England
Article Number
254
Date Publish Online
2025-12-05