Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in seropositive solid organ transplant recipients: anti-AD2 levels correlate with protection from viraemia

Abstract

The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase-2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased gB ELISA antibody levels whose titer correlated directly with protection against post-transplant viremia. The aim of the current study was to investigate in more detail this protective humoral response in vaccinated seropositive transplant recipients. We focussed on four key antigenic domains (AD) of gB; AD1, AD2, AD4 and AD5 measuring antibody levels in patient sera and correlating these with post-transplant HCMV viremia. Vaccination of seropositive patients significantly boosted pre-existing antibody levels against the immunodominant region AD1 as well as against AD2, AD4 and AD5. A decreased incidence of viremia correlated with higher antibody titers against AD2 but not with antibody titers against the other three ADs. Overall, these data support the hypothesis that antibodies against AD2 are a major component of the immune protection of seropositives seen following vaccination with gB/MF59 vaccine and identify a correlate of protective immunity in allograft patients