Background To date, no specific vaccine or drug has been proven to be effective against SARS-CoV-2 infection . Therefore, we implemented an immunoinformatic approach to design an efficient multi-epitopes vaccine against SARS-CoV-2 . Results The designed-vaccine construct consists of several immunodominant epitopes from structural proteins of spike, nucleocapsid, membrane, and envelope . These peptides promote cellular and humoral immunity and interferon-gamma responses . Also, these epitopes have a high antigenic capacity and are not likely to cause allergies . To enhance the vaccine immunogenicity, we used three potent adjuvants: Flagellin of subsp . enterica serovar Dublin, a driven peptide from high mobility group box 1 as HP-91, and human beta-defensin 3 protein . The physicochemical and immunological properties of the vaccine structure were evaluated . The tertiary structure of the vaccine protein was predicted and refined by Phyre2 and Galaxi refine and validated using RAMPAGE and ERRAT . Results of ElliPro showed 246 sresidues from vaccine might be conformational B-cell epitopes . Docking of the vaccine with toll-like receptors (TLR) 3 , 5 , 8, and angiotensin-converting enzyme 2 approved an appropriate interaction between the vaccine and receptors . Prediction of mRNA secondary structure and in silico cloning demonstrated that the vaccine can be efficiently expressed in . Conclusion Our results demonstrated that the multi-epitope vaccine might be potentially antigenic and induce humoral and cellular immune responses against SARS-CoV-2 . This vaccine can interact appropriately with the TLR3 , 5, and 8 . Also, it has a high-quality structure and suitable characteristics such as high stability and potential for expression in.