What long-term follow-up results do randomized controlled trials report for Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines through 12–24 months?
Executive summary
Randomized controlled trials of Pfizer–BioNTech (BNT162b2) and Moderna (mRNA‑1273) reported high short‑term efficacy (≈95% for BNT162b2 and ≈94% for mRNA‑1273) with safety data principally through about 2 months in the original publications and formal trial follow‑ups reporting results through six months; peer‑reviewed RCT follow‑ups and trial reports document durability of clinical efficacy up to 6 months and immunologic persistence up to 12 months in some subgroups, but randomized trial data through 12–24 months are not described in the provided sources [1] [2] [3] [4].
1. RCT headline efficacy and the follow‑up window
The pivotal, randomized, placebo‑controlled trials established the initial high efficacy: BNT162b2 showed about 95% efficacy ≥7 days after the second dose in the NEJM report of the Phase 3 trial (median ~2 months follow‑up in the published paper) [1] [5]. Moderna’s pivotal trial likewise reported about 94.1% efficacy with a median follow‑up of roughly 9 weeks post‑dose 2 in regulatory materials and FDA briefings [3] [6]. Those landmark RCT publications and company briefings therefore provide robust randomized evidence for short‑term protection but only short windows of blinded follow‑up in the primary reports [1] [3].
2. What the trial follow‑ups actually published: up to six months
Both manufacturers and peer‑reviewed follow‑up publications extended observation beyond the initial 2‑month snapshot: Pfizer/BioNTech published six‑month efficacy and safety results showing sustained high efficacy but with some gradual decline, describing favorable safety through six months after dose two [2] [7]. Moderna and other investigators similarly reported antibody persistence and immunologic durability through six months after the second dose in phase‑1/phase‑3 materials and NEJM/other reports [8] [6]. These six‑month RCT and trial‑cohort follow‑ups are the longest randomized‑trial substantiated clinical efficacy durations directly documented in the provided sources [2] [8].
3. Evidence beyond six months in trials and cohorts: immunogenicity and selected 12‑month data
The provided sources include trial‑linked and trial‑derived analyses that extend immunologic and observational data toward 12 months in selected populations. Moderna’s TeenCOVE adolescent trial reported immunogenicity up to 12 months in a long‑term analysis of participants (median follow‑up ~312 days for a subset), demonstrating antibody persistence and long‑term immunogenicity in adolescents [4]. An Oxford supplement study following health‑care workers after BNT162b2 vaccination tracked infections and immune markers through December 2022 and reports breakthrough rates over a multi‑year follow‑up, but this is an observational cohort tied to vaccine recipients rather than the original randomized, placebo‑controlled trial continuing blinded comparisons through 12–24 months [9]. Thus some trial‑linked immunologic data reach ~12 months, but randomized clinical endpoint data at that interval are not documented in the supplied material [4] [9].
4. What the supplied material does not show: randomized 12–24 month clinical endpoint RCT results
Available sources do not mention randomized, placebo‑controlled trial results reporting clinical vaccine efficacy outcomes (symptomatic infection, hospitalization, death) through 12–24 months post‑primary series for either BNT162b2 or mRNA‑1273. The landmark RCT reports and six‑month follow‑ups are explicit [1] [2] [3], and later documents and cohort studies extend observational or immunologic follow‑up, but the supplied records do not present blinded RCT efficacy results out to 12–24 months [4] [9]. Where longer intervals are referenced, they are trial continuation, cohort or immunogenicity analyses rather than fresh randomized endpoint readouts [9] [4].
5. Real‑world and observational data partially fill the gap — with caveats
The supplied materials include many observational and registry studies and programmatic analyses that estimate effectiveness of updated boosters and longer‑term outcomes (including nationwide Danish register work and US cohort studies), but these are nonrandomized and reflect changing variants, booster programs, and hybrid immunity — confounders that complicate direct attribution to the original RCT primary series across 12–24 months [10] [11] [12]. Those observational data inform policy and demonstrate continued benefit of updated and bivalent formulations, but they do not substitute for randomized, blinded long‑term RCT endpoint data [10] [13].
6. Bottom line for practitioners and policy watchers
Randomized controlled evidence from the pivotal trials and formal RCT follow‑ups documents high efficacy and acceptable safety through about six months for both vaccines [2] [3] [8]. Some trial‑derived immunogenicity and cohort analyses reach ~12 months in subgroups [4] [9]. The provided sources do not contain randomized clinical endpoint results reported through 12–24 months; longer‑term clinical effectiveness in that window is reported mainly via observational and programmatic studies rather than continued blinded RCT comparisons [9] [10] [11].