In silico design of multi-epitope vaccine candidate based on structural proteins of porcine reproductive and respiratory syndrome virus

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most common respiratory disease-causing viral agents. Swine infected with PRRSV exhibit severe respiratory symptoms and reproductive failure, leading to significant economic losses. To address this issue, inactivated and live-attenuated vaccines have been developed. However, the current commercially available PRRSV vaccines do not confer sufficient protection or have safety issues. The use of epitope-based subunit vaccines reduce safety risks by including only specific immunogenic portions of the antigens. To enhance immune protection, this study targeted multiple structural proteins of PRRSV, including GP2, GP3, GP4, GP5, membrane (M), envelope (E), GP5a, and nucleocapsid (N), to enable the discovery of novel epitopes. Thus, a reverse vaccinology approach was utilized to design a multi-epitope subunit vaccine construct against PRRSV. Using different tools, seven linear B cell, seven cytotoxic T cell, and three helper T cell epitopes were predicted to be safe, antigenic, and immunogenic. These epitopes were linked together, and a protein adjuvant, heparin-binding hemagglutinin, was added to increase the vaccine's immunogenicity. The construct was then docked to Toll-like receptor 4 (TLR4) to assess its ability to initiate the innate immune response. The final vaccine construct was determined to be antigenic, stable, non-allergenic, and soluble. Furthermore, the vaccine demonstrated stable binding to TLR4 based on coarse-grained and atomistic molecular dynamics simulations. Finally, the immune simulation of the vaccine construct showed a robust immune response against PRRSV. In this study, a candidate vaccine construct was successfully designed as a potential strategy against PRRSV.