Computational design of a legacy-based epitope vaccine against Human Cytomegalovirus

Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically-naive and immunosuppressed patient. The prevention, diagnosis and therapy of HCMV infection are thus crucial to public health. Despite the development of multiple prophylactic and pre-emptive therapeutic approaches, effective treatments remain a significant challenge. Thus, we sought to develop an epitope ensemble vaccine against HCMV by analyzing experimentally-defined HCMV-specific epitopes that effectively elicit B cell, CD4 T cell and CD8 T cell responses. The T cell component consists of 6 CD8 and 4 CD4 conserved T cell epitopes that were predicted to provide a population protection coverage over 90% and 80%. The B cell component consists of 2 B cell epitopes mapping onto glycoproteins L and H, respectively, which were selected by flexibility and solvent accessibility criteria. The proposed biological component makes this vaccine formulation not only multifunctional but also multi-antigenic, since it targets different early antigens that are vital for viral tropism, latency establishment, and replication. Here, we discuss the fundamental evidence supporting this approach and analyze its present limits