This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.