Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence

Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection (mRNA-1273: 86%, 95%CI: 81-90.6%; BNT162b2: 76%, 95%CI: 69-81%) and COVID-19 associated hospitalization (mRNA-1273: 91.6%, 95% CI: 81-97%; BNT162b2: 85%, 95% CI: 73-93%). In July, vaccine effectiveness against hospitalization has remained high (mRNA-1273: 81%, 95% CI: 33-96.3%; BNT162b2: 75%, 95% CI: 24-93.9%), but effectiveness against infection was lower for both vaccines (mRNA-1273: 76%, 95% CI: 58-87%; BNT162b2: 42%, 95% CI: 13-62%), with a more pronounced reduction for BNT162b2. Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.