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

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.