Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients

Abstract

A human cytomegalovirus (HCMV) vaccine is urgently needed to protect against primary infection and enhance existing immunity in HCMV-infected individuals (HCMV+). Using sera from HCMV+ glycoprotein B/MF59 vaccine recipients prior to transplant, we investigated the composition of the immune response. Vaccination boosted preexisting humoral responses in our HCMV+ cohort but did not promote de novo responses against novel linear epitopes. This suggests that prior natural infection has a profound effect on shaping the antibody repertoire and subsequent response to vaccination ("original antigenic sin"). Thus, vaccination of HCMV+ may require strategies of epitope presentation distinct from those intended to prevent primary infection.