Effectiveness of mRNA-1273 against Delta, Mu, and other emerging variants

BackgroundReal-world studies have found high vaccine effectiveness (VE) of mRNA-based COVID-19 vaccines, but reduced VE against the Delta variant and waning protection have been reported, with few studies examining mRNA-1273 variant-specific VE.MethodsWe conducted a test-negative case-control study at Kaiser Permanente Southern California. Whole genome sequencing was conducted for SARS-CoV-2 positive specimens collected from 3/1/2021 to 7/27/2021. Test-positive cases were matched 1:5 to test-negative controls on age, sex, race/ethnicity, and specimen collection date. Outcomes included SARS-CoV-2 infection and hospitalization. Exposures were 2 doses or 1 dose of mRNA-1273 ≥14 days prior to specimen collection versus no COVID-19 vaccination. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, adjusting for confounders. VE was calculated as (1-odds ratio)x100%.ResultsThe study included 8,153 cases and their matched controls. Two-dose VE (95% confidence interval) was 86.7% (84.3-88.7%) against Delta infection, 98.4% (96.9-99.1%) against Alpha, 90.4% (73.9-96.5%) against Mu, 96-98% against other identified variants, and 79.9% (76.9-82.5%) against unidentified variants. VE against Delta declined from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection.ConclusionsTwo doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants. However, VE against Delta moderately declined with increasing time since vaccination.Trial Registration NumberNot applicableFundingModerna Inc.