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Background: The recent COVID vaccinations have successfully reduced death and severity but did not stop the transmission of viruses by the emerging SARS-CoV-2 strain. There is a need for better and long-lasting dynamic vaccines for numerous prevailing strains and the evolving SARS-CoV-2 virus, necessitating the development of broad-spectrum strains being used to stop infection by reducing the spread rate and re-infection. The spike (S) glycoprotein is one of the proteins expressed commonly in the early phases of SARS-CoV-2 infection. It has been identified as the most immunogenic protein of SARS-CoV-2., Methods: In this study, advanced bioinformatics techniques have been exploited to design the novel multi-epitope vaccine using conserved S protein portions from widespread strains of SARS-CoV-2 to predict B cell and T cell epitopes. These epitopes were selected based on toxicity, antigenicity score and immunogenicity. Epitope combinations were used to construct the maximum potent multi-epitope construct with potential immunogenic features. EAAAK, AAY, and GPGPG were used as linkers to construct epitopes., Results: The developed vaccine has shown positive results. After the chimeric vaccine construct was cloned into the PET28a (+) vector for expression screening in Escherichia coli , the potential expression of the construct was identified., Conclusion: The construct vaccine performed well in computer-based immune response simulation and covered a variety of allelic populations. These computational results are more helpful for further analysis of our contract vaccine, which can finally help control and prevent SARS-CoV-2 infections worldwide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)