Building Resilient Immunity Against Powassan Virus: The Necessity of A Comprehensive Immunoinformatic Approach and Coordinated T and B Cell Responses

Background: Powassan virus (POWV), a vector-borne pathogen primarily impacting humans as incidental hosts, has recently surfaced as a significant worldwide health concern, carrying the potential for severe clinical consequences or enduring neurological sequelae. Currently, there are no approved vaccines for POWV. The key to developing effective vaccines lies in identifying protective factors. Despite significant outbreaks and the absence of antiviral treatments, progress in creating an epitope-based vaccine for POWV has been slow. Aim of the work: Our aim was to employ various immunoinformatics and docking simulation methods to design an epitope-based vaccine capable of triggering a robust immune response and predict inhibitors that could potentially target therapeutic sites effectively. Methodology: At first, the complete POWV proteome was obtained from a database and scrutinized to identify the protein with the highest immunogenicity. The structural attributes of the designated protein were thoroughly explored. Subsequently, the chosen protein underwent testing to assess its capacity to stimulate both humoral and cell-mediated immunity through T and B cells. Results: The leading B cell and T cell epitopes were pinpointed as a peptide segment encompassing 7 amino acids from position 353 to 360, represented by the sequence TLAGPRSKY. This peptide exhibited the potential to interact with up to 19 different HLAs, offering extensive population coverage that ranged from 62.53% to 86.97%. To confirm the binding interaction within the HLA binding cleft, we conducted in-silico docking techniques. Furthermore, we assessed the allergenicity of these epitopes. In our post-therapeutic approach, we predicted the three-dimensional structure, conducted validation and verification processes, and subsequently performed molecular docking studies to identify potential drug-binding sites and suitable therapeutic inhibitors for the target protein. Conclusion: Nevertheless, this computational approach to epitope-based peptide vaccine design and target site prediction against POWV represents a pioneering advancement in Powassan virus research. It's important to note that the outcomes will require validation through in vitro and in vivo trials.