Abstract
Despite the rapid development of SARS-CoV-2 mRNA vaccines to combat the Coronavirus
infectious disease 2019 (COVID-19) pandemic, vaccine hesitancy gained traction as the
pandemic continued. Among the widely discussed topics related to the COVID-19 mRNA
vaccines, DNA contamination cast doubt on the quality of the product and may have undermined
public trust. Here, we report a simple method to detect residual replication-competent plasmid
DNA that is present in mRNA vaccines as impurities. Using 4 vials of experimental mRNA
vaccines, we found that two out of four vials of those experimental mRNA vaccines contained
residual plasmid DNA that transformed Escherichia coli cells. We subsequently applied our
method to assess 2 separate lots of Pfizer COVID-19 mRNA vaccines and found no replication-
competent plasmid DNA. However, these authorized vaccines do contain residual DNA to a
level that exceeds 10 ng per dose. Our results suggest that stringent and transparent monitoring
of DNA impurity may aid in the buildup of public trust in mRNA vaccines.