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Volume 104, Issue 6

A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients’ sera Open Access

Abstract

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) – a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cytomegalovirus , glycoprotein B , neutralizing antibodies and vaccine
Funding
This study was supported by the:
  • Rosetrees Trust (Award A2207)
    • Principle Award Recipient: MatthewB Reeves
  • Rosetrees Trust (Award A1601)
    • Principle Award Recipient: MatthewB Reeves
  • Wellcome Trust (Award WT204870/Z/16/Z)
    • Principle Award Recipient: PaulD Griffiths
  • Wellcome Trust (Award WT204870/Z/16/Z)
    • Principle Award Recipient: MatthewB Reeves
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-06-13
2024-04-28
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A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients’ sera
J. Gen. Virol. 104, 001860 (2023); https://doi.org/10.1099/jgv.0.001860
/content/journal/jgv/10.1099/jgv.0.001860
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