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Hung Fu Tseng, Bradley K. Ackerson, Katia J. Bruxvoort, Lina S. Sy, Julia E. Tubert, Gina S. Lee, Jennifer H. Ku, Ana Florea, Yi Luo, Sijia Qiu, Soon Kyu Choi, Harpreet S. Takhar, Michael Aragones, Yamuna D. Paila, Scott Chavers, Carla A. Talarico, and Lei Qian
January 12, 2023
Nature Communications
Kaiser Permanente Southern California

Abstract: Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against Omicron BA.4/BA.5 compared with earlier Omicron subvariants. We conducted a test-negative case–control study evaluating mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron subvariants. The study included 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022…

Results: … In analyses of 3-dose VE (versus unvaccinated) against infection with Omicron subvariants by time since vaccination, the 3-dose VE against BA.1 ranged from 85.8% (95% confidence interval [CI] 82.7%, 88.3%) in the 14-30 days after the third dose to 54.9% (95% CI 35.6%, 68.4%) >150 days after the third dose (Fig. 2, Supplementary Table 2a). VE for these two time intervals, respectively, was 61.0% (95% CI 27.6%, 79.0%) and -24.9% (95% CI -32.3%, -16.7%) for BA.2, excluding BA.2.12.1; 82.7% (95% CI 44.2%, 94.7%) and -26.8% (95% CI -34.6%, -18.0%) for BA.2.12.1; 72.6% (95% CI - 54.7%, 96.6%) and -16.4% (95% CI -35.8%, 8.2%) for BA.4; and 90.6% (95% CI 30.6%, 98.7%) and -17.9% (95% CI -29.6%, -4.2%) for BA.5. We also present the relative VE (rVE) comparing 3 doses to 2 doses against Omicron subvariants by time since vaccination (Fig. 2, Supplementary Table 2b). In general, we observed consistent incremental protection of 3 doses versus 2 doses in the 14-90 days after the third dose, other than against BA.4, which had a small number of cases and wide CI. The incremental benefit in protection decreased by time since the third dose. For BA.5, the 95% CI of rVE included 0 after >90 days after the third dose.”

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