Abstract: As the single-stranded RNA virus with the longest gene, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)inherits the ability of mutation, while evolving a unique proof-reading capacity to keep stability of its long genome during replication. Mutations frequently occur in spike protein to enable cell entry and immune escape, which result in emergence of more adaptable variants to maintain its transmission. Vaccination against SARS-CoV-2 can effectively reduce infection, transmission, hospitalization and death. However, a growing number of studies and real-world data have shown that the immune protection induced by vaccination and natural infection wanes rapidly. Coupled with the emergence of immune-escape viral strains, control of COVID-19 epidemic is still a challenge. Here the dynamics of SARS-Cov-2 viral mutation and effectiveness of vaccination are reviewed, with a prospect of the prevention and control of epidemic of SARS-CoV-2.