Abstract The association between vaccine efficacy (VE) and force of infection (FoI) remains incompletely understood . Previous analyses have been primarily based on trial-level summary data—not accounting for the effect of time and constrained by the number of trials. Here, we leverage individual-level data from three phase 3 randomized, placebo-controlled COVID-19 vaccine trials —the COVE trial (Moderna, CoVPN3001), the AZD1222 trial (AstraZeneca, CoVPN3002), and the ENSEMBLE trial (Janssen/Johnson & Johnson, CoVPN3003)—and contemporaneous geographic-location-specific SARS-CoV-2 surveillance data from the start of the pandemic through November 14, 2021 (including the blinded follow-up periods of the trials) to conduct five cohort- and vaccine-specific analyses: COVE (U.S.), AZD1222 overall (U.S. + non-U.S.), AZD1222 U.S., ENSEMBLE overall (U.S. + non-U.S.), and ENSEMBLE U.S. In AZD1222 U.S., higher VE was associated with higher FoI (p = 0.01). In ENSEMBLE overall, lower VE w...
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