Cross-herpesvirus immunity of the cytomegalovirus gB/MF59 vaccine response

Lankina A, Hargreaves A, Lui WT, Kropff B, Wei A, Breuer J, White RE, Thomas M, Griffiths PD, Reeves MB (2025)

Publication Type: Journal article

Publication year: 2025

Journal

npj Vaccines Springer Nature

Book Volume: 10

Article Number: 254

Journal Issue: 1

DOI: 10.1038/s41541-025-01315-6

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.

Authors with CRIS profile

Marco Thomas Institute of Clinical and Molecular Virology

Involved external institutions

University College London (UCL) GB United Kingdom (GB) Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB)

How to cite

APA:

Lankina, A., Hargreaves, A., Lui, W.T., Kropff, B., Wei, A., Breuer, J.,... Reeves, M.B. (2025). Cross-herpesvirus immunity of the cytomegalovirus gB/MF59 vaccine response. npj Vaccines, 10(1). https://doi.org/10.1038/s41541-025-01315-6

MLA:

Lankina, A., et al. "Cross-herpesvirus immunity of the cytomegalovirus gB/MF59 vaccine response." npj Vaccines 10.1 (2025).

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