Comparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines

The optimal interval between the first and second doses of COVID-19 mRNA vaccines has not been thoroughly evaluated. Employing a target trial emulation approach, we compared the effectiveness of different interdose intervals among >6 million mRNA vaccine recipients in Georgia, USA, from December 2020 to March 2022. We compared three protocols defined by interdose interval: recommended by the Food and Drug Administration (FDA) (17-25 days for Pfizer-BioNTech; 24-32 days for Moderna), late-but-allowable (26-42 days for Pfizer-BioNTech; 33-49 days for Moderna), and late ( ≥ 43 days for Pfizer-BioNTech; ≥50 days for Moderna). In the short-term, the risk of SARS-CoV-2 infection was lowest under the FDA-recommended protocol. Longer-term, the late-but-allowable protocol resulted in the lowest risk (risk ratio on Day 120 after the first dose administration compared to the FDA-recommended protocol: 0.83 [95% confidence interval: 0.82-0.84]). Here, we showed that delaying the second dose by 1-2 weeks may provide stronger long-term protection.