Efficacy and Safety of a Booster Regimen of Ad26.COV2.S Vaccine against Covid-19

  1. Karin Hardt
  2. An Vandebosch
  3. Jerry Sadoff
  4. Mathieu Le Gars
  5. Carla Truyers
  6. David Lowson
  7. Ilse Van Dromme
  8. Johan Vingerhoets
  9. Tobias Kamphuis
  10. Gert Scheper
  11. Javier Ruiz-Guiñazú
  12. Saul N. Faust
  13. Christoph D. Spinner
  14. Hanneke Schuitemaker
  15. Johan Van Hoof
  16. Macaya Douoguih
  17. Frank Struyf
  18. the ENSEMBLE2 Study Group
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Abstract

Background

Despite the availability of effective vaccines against coronavirus disease 2019 (Covid-19), the emergence of variant strains and breakthrough infections pose a challenging new reality. Booster vaccinations are needed to maintain vaccine-induced protection.

Methods

ENSEMBLE2 is an ongoing, randomized, double-blind, placebo-controlled, phase 3 pivotal trial including crossover vaccination after emergency authorization of Covid-19 vaccines. Adults aged ≥18 years were randomized to receive Ad26.COV2.S or placebo as a primary dose plus a booster dose at two months. The primary endpoint was vaccine efficacy against the first occurrence of molecularly-confirmed moderate to severe–critical Covid-19 with onset ≥14 days after booster vaccination in the per-protocol population. Key efficacy, safety, and immunogenicity endpoints were also assessed.

Results

The double-blind phase enrolled 31,300 participants, 14,492 of whom received 2 doses and were evaluable for efficacy (per-protocol set, Ad26.COV2.S n=7484; placebo n=7008). Baseline demographics and characteristics were balanced. Vaccine efficacy was 75.2% (adjusted 95% CI, 54.6-87.3) against moderate to severe–critical Covid-19 and was similar against symptomatic infection (75.6% [55.5-99.9]). Efficacy was consistent across participants with and without comorbidities, and reached 93.7% (58.5-99.9) in the US. Vaccine efficacy against severe–critical Covid-19 was 100% (32.6-100.0; 0 vs 8 cases). The booster vaccine induced robust humoral responses and exhibited an acceptable safety profile.

Conclusions

A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults led to high vaccine efficacy, including against any symptomatic infection and SARS-CoV-2 variants prevalent during the study. (Funding: Janssen Research and Development and others; ENSEMBLE2 <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> number, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04614948">NCT04614948</ext-link> .)

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