Immuno-informatics approach to design a multi-epitope vaccine to combat cytomegalovirus infection

Human cytomegalovirus (HCMV) poses a serious public health problem causing morbidity and mortality in transplant recipients, immunocompromised patients, and congenitally infected newborns. Considering the recent reports of emergence of Ganciclovir drug resistance, vaccine development is the need of an hour. In the present study, a multi-epitope vaccine was constructed targeting the major hotspot- the pentavalent complex of glycoproteins (H/L/UL128-UL130-UL131) of HCMV, and other important target proteins- gB and pp65. The vaccine designed was composed of series of epitopes belonging to CD4, CD8 and B cells. As an immunobooster, the CpG motifs was linked to the vaccine which severed as an adjuvant. The affinity, stability and flexibility of the vaccine construct with the immune receptor- Toll like receptor -9 (TLR-9) was investigated by molecular docking and molecular dynamics simulations. The in-silico immune simulations of the vaccine sequence were also carried out to determine its ability to stimulate different immune components. Further, an in-silico cloning of the vaccine construct was performed to analyze the feasibility of its expression and translation efficiency in pET-28a (+) vector. The overall results obtained indicated the vaccine to be immunogenic, non-allergic, had high population coverage, high affinity and stability with the immune receptor, had efficient expression in host E. coli and was effective in stimulating different immune cell types like T helper, T cytotoxic, B cells, dendritic cells, macrophages and interleukins. The proposed vaccine construct is expected to be highly efficacious and needs to be carried forward by the vaccinologists to test its efficacy in lab settings.