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The importance of understanding SARS-CoV-2 evolution cannot beoveremphasized. Recent studies confirm that natural selection is the dominatingmechanism of SARS-CoV-2 evolution, which favors mutations that strengthen viralinfectivity. We demonstrate that vaccine-breakthrough or antibody-resistantmutations provide a new mechanism of viral evolution. Specifically,vaccine-resistant mutation Y449S in the spike (S) protein receptor-bondingdomain (RBD), which occurred in co-mutation [Y449S, N501Y], has reducedinfectivity compared to the original SARS-CoV-2 but can disrupt existingantibodies that neutralize the virus. By tracing the evolutionary trajectoriesof vaccine-resistant mutations in over 1.9 million SARS-CoV-2 genomes, wereveal that the occurrence and frequency of vaccine-resistant mutationscorrelate strongly with the vaccination rates in Europe and America. Weanticipate that as a complementary transmission pathway, vaccine-resistantmutations will become a dominating mechanism of SARS-CoV-2 evolution when mostof the world's population is vaccinated. Our study sheds light on SARS-CoV-2evolution and transmission and enables the design of the next-generationmutation-proof vaccines and antibody drugs.

The evolution of the mechanisms of SARS-CoV-2 evolution revealing vaccine-resistant mutations in Europe and America