1939. Who to Boost When: An Analysis of Dosing Interval and Age on COVID-19 Outcomes in the COVE Trial During the Delta and Omicron Waves

BACKGROUND: The effects of age and interval between vaccine doses on COVID-19 are incompletely understood, yet critical for public health policy. METHODS: This analysis evaluated the effectiveness of an mRNA-1273 50 μg booster (3(rd) dose) in ∼17,000 boosted participants in the phase 3 coronavirus efficacy (COVE) trial who previously received 2-doses of 100 µg mRNA-1273 during the randomized placebo-controlled phase (mRNA-1273, 1st dose July-Oct 2020), or open label phase (placebo-mRNA-1273, 1st dose Dec 2020-Apr 2021). A single 50 µg mRNA-1273 (original vaccine) booster was administered starting Sep 2021. The effect of boosting on COVID-19 risk was assessed in Cox models by the initially randomized arm, time since booster, and age groups (< 65, ≥ 65) between Sep 2021-May 2022 during the open label phase of COVE. RESULTS: The median dosing intervals (IQR) between primary series and booster were 8.2 (7.8-8.7) months for the placebo-mRNA-1273 and 12.9 (12.3-13.5) months for the mRNA-1273 arms. A booster dose provided substantial additional protection against COVID-19 during the Delta wave through 60 days and was high for Omicron (BA.1), then waned over time by 110 days (Figure). The risk of Omicron COVID-19 post booster was lower by 24% (95% CI: 16%, 32%) in the mRNA-1273 vs the placebo-mRNA arm indicating possible benefit of longer boost interval. In a separate analysis, among participants ≥ 65 years, the initial booster (95% CI) efficacy against Omicron was 86% (69%, 93%) which waned to 28% (-47%, 65%) after ∼4 months. For those < 65 years, the analogous estimates were 50% (36%, 61%) and 6% (-29%, 31%), indicating a larger boosting effect in those ≥ 65 years. When further stratified by arm, for those ≥ 65 years, the initial boost efficacy against Omicron was 79% (41%, 92%) for the placebo-mRNA arm and 91% (79%, 96%) for mRNA-1273. For those < 65, the analogous estimates were 52% (30%, 62%) and 55% (39%, 66%), suggesting the effect of booster interval was largely concentrated in those ≥ 65 years. [Figure: see text] CONCLUSION: Boosting with mRNA-1273 provided additional COVID-19 protection during the Delta and Omicron variant waves. Overall, boosting reduced the risk of Omicron COVID-19 but waned over time (∼4 months). The effects of boosting and interval were more pronounced in those ≥ 65 years of age. DISCLOSURES: Xiaowei Wang, PhD, Moderna, Inc.: Stocks/Bonds Peter Gilbert, PhD, NIH NIAID: Grant/Research Support Lindsey R. Baden, MD, NIH/NIAID: Grant/Research Support Hana M. El Sahly, MD, NIH and/or NIAID: Grant/Research Support Holly Janes, PhD, National Institutes of Health: Grant/Research Support Weiping Deng, PhD, Moderna, Inc.: Stocks/Bonds Frances Priddy, MD, MPH, Moderna, Inc.: Stocks/Bonds|Moderna, Inc.: Stocks/Bonds Avika Dixit, MBBS, Moderna, Inc.: Stocks/Bonds Joanne Tomassini, Ph.D., Moderna, Inc.: Advisor/Consultant Rituparna Das, M.D., Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Jacqueline Miller, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Honghong Zhou, Ph.D., Moderna, Inc.: Stocks/Bonds