Towards an Ensemble Vaccine against the Pegivirus Using Computational Modelling Approaches and Its Validation through In Silico Cloning and Immune Simulation

Abstract

Pegivirus, HPgV, which was earlier known as Gb virus and hepatitis G virus, is an enveloped, positive-stranded RNA and lymphotropic virus classified into the Flaviviridae family. The transmission routes primarily involve blood products, and infections are worldwide, leading up to 25% of persistent infections. To date, no effective therapeutic means are available to clear Pegivirus infections. Effective vaccine therapeutics is the best alternative to manage this disease and any associated potential pandemic. Thus, whole proteome-based mining of immunogenic peptides, i.e., CTL (cytotoxic T lymphocytes), HTL (helper T lymphocytes), and B cell epitopes, was mapped to design a vaccine ensemble. Our investigation revealed that 29 different epitopes impart a critical role in immune response induction, which was also validated by exploring its physiochemical properties and experimental feasibility. In silico expression and host immune simulation were examined using an agent-based modeling approach and confirmed the induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.

Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation

“…After the initial attack of the infectious agent, acquired immunity in humans produces memory cells that recognize the pathogens on subsequent attacks. These memory cells provide the basis for the development of a vaccine against specific pathogens ( 40 , 41 ). Therefore, in the present study, we used immunoinformatic approaches to develop a MESVs to boost acquired immunity against the monkeypox virus.…”

Targeted Protein-Specific Multi-Epitope-Based Vaccine Designing against Human Cytomegalovirus by Using Immunoinformatics Approaches

“…JCat determines the GC content and CAI score of the constructed vaccine to optimize the reversely transcribed vaccine construct in a bacterial expression system [ 53 ]. The EcoRI and XhoI, restriction enzymes were manually inserted into the vaccine sequence, and the sequence was subsequently cloned onto the pET-28a (+) plasmid using Snapgene software [ 54 ].…”

Structural vaccinology-based design of multi-epitopes vaccine against Streptococcus gordonii and validation using molecular modeling and immune simulation approaches

“…The server allocates the IC50 value to the epitopes, which has an inverse relation with the binding affinity towards MHC-II. IC50 score of less than 50 nM constitutes high binding affinity, a score less than 500 nM is determined as intermediate binding affinity and less than 5000 nM as low binding affinity [ 23 ]. Moreover, the HTL epitopes were selected based on a low percentile rank that indicates their high binding affinity.…”

“…Streptococcus gordonii expressing M6-Sj-F1 fusion protein protected mice from infection caused by Schistosoma japonicum [ 22 ]. Therefore, the best alternative treatment is a vaccine which is reported to save millions of lives yearly [ 23 ]. Numerous molecular-omics tools were exploited to mine immunogenic peptides, i.e., T-cell and B-cell epitopes, and construct a vaccine sequence.…”