Original antigenic sin shapes the immunological repertoire evoked by HCMV gB-MF59 vaccine in seropositive recipients

A cytomegalovirus (CMV) vaccine is urgently needed to protect against primary infection and enhance existing immunity in CMV infected individuals (CMV+). Using sera from CMV+ gB/MF59 vaccine recipients prior to transplant we investigated the composition of the immune response. Vaccination boosted pre-existing humoral responses in our CMV+ 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 CMV+ may require strategies of epitope presentation distinct from those intended to prevent primary infection.