Objective To analyze the genetic and evolutionary properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF 1ab/S/M proteins and select antigen epitope sequences of mRNA vaccines. Methods We analyzed the worldwide SARS-CoV-2 genome sequences in this study and have focused on the protein and nucleic acid sequences of the ORF 1ab/S/M. The neighbor-joining tree was employed to map the global distribution of genetic differences. Based on current research on SARS-CoV-2 and SARS-CoV-2 genetic differences, we predicted candidate mRNA vaccines for SARS-CoV-2. Results The SARS-CoV-2 ORF 1ab nucleic acid sequence similarity is 100.0%, while the homology is 99.3% in the global hot region; the S-protein nucleic acid sequence similarity is 100.0%, while the homology is 97.5%; the M-protein nucleic acid sequence similarity is 100.0%, while the homology is 99.9%. Global distribution of ORF 1ab/S/M proteins indicates that there is a significant genetic difference between the Americas and Eurasia. Potential vaccine antigen epitope mRNA sequences (11 B cell responses and 13 T cell responses) were selected for SARS-CoV-2 ORF 1ab protein; 6 B cell responses and 4 T cell responses antigen epitope mRNA sequences were selected for the Spike protein; 3 B cell responses and 7 T cell responses antigen epitope mRNA sequences were selected for the membrane protein. Conclusion There are significant genetic differences in the global hot spot of SARS-CoV-2 in the Americas and Eurasia. Through our new antigen design strategy to screen linear epitopes, we predicted many sequences in ORF 1ab/S/M coding region that potentially raising an immune response. Our study will benefit the discovery of the mRNA vaccine (tandem antigen epitope sequence), antibody discovery, and potentially understanding related immune mechanisms. DOI: 10.11855/j.issn.0577-7402.2020.11.04