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Vaccines play an essential role in controlling the rates of fatality and morbidity. Vaccines not only arrest the beginning of different diseases but also assign a gateway for its elimination and reduce toxicity. This review gives an overview of the possible uses of computational tools for vaccine design. Moreover, we have described the initiatives of utilizing the diverse computational resources by exploring the immunological databases for developing epitope-based vaccines, peptide-based drugs, and other resources of immunotherapeutics. Finally, the applications of multi-graft and multivalent scaffolding, codon optimization and antibodyomics tools in identifying and designing in silico vaccine candidates are described.