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Gomes, Ariane, Baraniak, Ilona, McIntosh, Megan, Sodi, Isabella, Langstone, Tony, Siddiqui, Saima, Atkinson, Claire, McLean, Gary R., Griffiths, Paul D. and Reeves, Matthew B. (2023) A temperature-dependent virus-binding assay reveals the presence of neutralising antibodies in human cytomegalovirus gB vaccine recipients’ sera. Journal of General Virology, 104 (6). pp. 1-12. ISSN 1465-2099
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 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-neutralising antibodies that target cell associated virus which is concomitant with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay which promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB vaccinated patients which cannot be detected using standard assays. We go on to show that this is not a general feature of gB neutralizing antibodies suggesting 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 vivo in transplant recipients their identification demonstrate the utility of the approach in identifying these responses. We hypothesise that further characterization has the potential to aid the identification of functions within gB 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.
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