Specificity and functional humoral immune responses induced by the VBI-1501A eVLP HCMV gB vaccine compared to the gB/MF59 vaccine

Connors, Megan R., Karthigeyan, Krithika P., Fuller, Adelaide S., Mitchell, Libby, Preston, Hannah, Ananyev, Sergey, Crooks, Chelsea M., Stanton, Richard ORCID: https://orcid.org/0000-0002-6799-1182, Anderson, David E. and Permar, Sallie R. 2025. Specificity and functional humoral immune responses induced by the VBI-1501A eVLP HCMV gB vaccine compared to the gB/MF59 vaccine. Human Vaccines & Immunotherapeutics 21 (1) , 2564555. 10.1080/21645515.2025.2564555

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Abstract

Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects globally yet has no licensed vaccine. Though some HCMV glycoprotein B (gB)-based vaccine candidates, such as the MF59-adjuvanted gB vaccine (gB/MF59) elicited limited virus neutralization, enveloped virus-like particle (eVLP) expression of gB induced robust CMV-neutralizing antibodies in a phase I trial in CMV-seronegative participants. Here, we further characterize the anti-gB binding and functional antibody responses induced by the VBI1501A gB eVLP vaccine in comparison to gB/MF59, the leading clinically tested vaccine to date. VBI1501A vaccination induced higher IgG binding to antigenic domains (AD) that are neutralizing antibody targets, AD-4 and AD-4+5, compared to the gB/MF59 vaccine, but elicited lower IgG binding to gB full-length and ectodomain. VBI1501A-elicited IgG responses showed no binding to the linear neutralizing domain AD-2 and elicited minimal binding to the AD-6 domain associated with viral cell-associated spread. While VBI1501A did not elicit IgG that bound to the clade-matched strain nor antibody-dependent cellular cytotoxicity responses, plasma IgG binding to cell associated gB and antibody dependent cellular phagocytosis responses were higher compared to the gB/MF59 vaccine. This study offers insight into strategies to improve on vaccine design of partially successful gB-containing HCMV vaccines.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Publisher:	Taylor and Francis Group
ISSN:	2164-5515
Funders:	Wellcome
Date of First Compliant Deposit:	25 September 2025
Date of Acceptance:	18 September 2025
Last Modified:	25 Sep 2025 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/181331

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