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Abstract
BackgroundHuman Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically naive and immunosuppressed patients. The prevention, diagnosis and therapy of HCMV infection are thus crucial to public health. The availability of effective prophylactic and therapeutic treatments remain a significant challenge and no vaccine is currently available. Here, we sought to define an epitope-based vaccine against HCMV, eliciting B and T cell responses, from experimentally defined HCMV-specific epitopes.ResultsWe selected 398 and 790 experimentally validated HCMV-specific B and T cell epitopes, respectively, from available epitope resources and apply a knowledge-based approach in combination with immunoinformatic predictions to ensemble a universal vaccine against HCMV. The T cell component consists of 6 CD8 and 6 CD4 T cell epitopes that are conserved among HCMV strains. All CD8 T cell epitopes were reported to induce cytotoxic activity, are derived from early expressed genes and are predicted to provide population protection coverage over 97%. The CD4 T cell epitopes are derived from HCMV structural proteins and provide a population protection coverage over 92%. The B cell component consists of just 3 B cell epitopes from the ectodomain of glycoproteins L and H that are highly flexible and exposed to the solvent.ConclusionsWe have defined a multiantigenic epitope vaccine ensemble against the HCMV that should elicit T and B cell responses in the entire population. Importantly, although we arrived to this epitope ensemble with the help of computational predictions, the actual epitopes are not predicted but are known to be immunogenic.
Highlights
Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population
HCMV amino acid sequence variability Compared to other organisms, viruses have a high replication rate, displaying great sequence variability
We first clustered all HCMV protein sequences (50,623) around a reference HCMV genome (NC_006273), obtaining representative protein clusters (162) for all but 9 of the open reading frames (ORFs) included in the selected reference HCMV genome
Summary
Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically naive and immunosuppressed patients. We sought to define an epitope-based vaccine against HCMV, eliciting B and T cell responses, from experimentally defined HCMVspecific epitopes. Human Cytomegalovirus (HCMV) seroprevalence is 50– 90% in the adult population. HCMV can be transmitted via saliva, sexual contact, placental transfer, breastfeeding, blood transfusion, solid-organ transplantation or hematopoietic stem cell transplantation. The main risk factors for HCMV infection, reactivation and disease are: immune-naive state, immunosuppressive regimens, organ transplants and co-infection [1]. The prevalence of HCMV, or human herpesvirus 5, is a beta herpesvirus consisting of a 235 Kpb double-stranded linear DNA core. HCMV genome is among the longest and most complex genomes of all human viruses, due to the diversity of wildtype strains in intrahost and interhost HCMV populations.
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