Ad-gBCMVpoly: A novel chimeric vaccine strategy for human cytomegalovirus-associated diseases

摘要

In spite of numerous attempts at successful licensure, a human cytomegalovirus (HCMV) vaccine formulation remains elusive. To overcome the limitations of previous strategies, we have recently developed a novel chimeric vaccine which allows induction of both humoral and cellular immune response following a single vaccination. This vaccine includes the extracellular domain of HCMV-encoded glycoprotein-B (gB) covalently linked to multiple HLA class I- and class II-restricted T-cell epitopes from multiple HCMV antigens as a contiguous polypeptide in a replication-deficient adenoviral vector Ad5/F35 (referred to as Ad-gBCMVpoly). Immunisation with Ad-gBCMVpoly consistently generated strong gB-specific neutralizing antibody and a broad range of HCMV-specific pluripotent CD8+ and CD4+ T-cells. This immunity suppressed infection with recombinant vaccinia virus encoding HCMV antigens. Furthermore, in vitro stimulation with Ad-gBCMVpoly rapidly expanded multiple antigen-specific human CD8+ and CD4+ T-cells from healthy virus carriers. Here we discuss the advantages of the Ad-gBCMVpoly vaccine and its potential application in different clinical settings.