Vaccines worldwide reduce severe coronavirus disease 2019 (COVID-19) consequences; however, viral evolution escapes immunity, raising global concerns about vaccine protection and requiring monitoring. Bioinformatics is crucial for studying vaccine escape, speeding up variant detection, mapping antibody evasion epitopes and ensuring updated vaccines and public health responses. This study combines bibliometric analysis of the Scopus literature (n = 416) on SARS-CoV-2 immune evasion using bioinformatics tools with descriptive analysis of the top ten most highly cited original articles. Our results showed the United States (USA) as the dominant contributor, leading in publication output, citation impact and collaboration networks. The key themes identified were immune evasion, spike protein mutations, and viral evolution, highlighting the structural, functional and immune evasion mechanisms of spike mutations. Leading authors and journals reveal a globally connected research community that is making advances in our understanding of SARS-CoV-2 vaccine evasion, and supporting the development of future treatments and vaccines. The top ten articles showed molecular docking, dynamics simulations, and protein modeling as crucial to studying vaccine escape. In conclusion, global research led mainly by the USA and supported by active contributions has used bioinformatics to elucidate SARS-CoV-2 immune evasion, guiding variant future vaccine and treatment development, variant monitoring, and preparedness for emerging variants.