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Publications

Journal Article Ahead of print

PubMed: 42364277 DOI: 10.1016/j.vaccine.2026.128769

A prematurely terminated phase 2, randomised trial to evaluate immunogenicity and reactogenicity of a single versus two-dose primary vaccination regimen of the mRNA vaccine BNT162b2 in previously SARS-CoV-2 infected children 5-11 years old (CoVacc trial).

Vaccine 88:128769

Authors: Cristina Prat-Aymerich, Lusine Yeghiazaryan, Rishi Delan Pathirana, Virginie Gautier, Alejandro Abner Garcia Leon, Gurvin Saini, Katherine Loens, Rebecca Jane Cox, Elisa Formiconi, Sophie O'Reilly, Karen van Hulst, Jeri Nijland, Oliver A Cornely, Patrick Mallon, Martin Posch, Patricia Bruijning-Verhagen

Affiliations

  • Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht University, Utrecht, the Netherlands; Ecraid Foundation, Utrecht, Netherlands.
  • Medical University of Vienna, Center for Medical Data Science, Institute of Medical Statistics, Spitalgasse 23, 1090 Vienna, Austria.
  • Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway and Influenza Centre, Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
  • Centre for Experimental Pathogen Host Research, University College Dublin Belfield, Dublin, Ireland; School of Medicine, University College Dublin Belfield, Dublin, Ireland. Conway Institute, University College Dublin Belfield, Dublin, Ireland.
  • Centre for Experimental Pathogen Host Research, University College Dublin Belfield, Dublin, Ireland.
  • LAB-Net, Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
  • Ecraid Foundation, Utrecht, Netherlands.
  • University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Division of Infectious Diseases, Excellence Center for Medical Mycology (ECMM), and Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), Cologne, Germany.
  • Centre for Experimental Pathogen Host Research, University College Dublin Belfield, Dublin, Ireland; School of Medicine, University College Dublin Belfield, Dublin, Ireland. St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
  • Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht University, Utrecht, the Netherlands.

Abstract

BACKGROUND

This open-label randomised phase 2 study aimed to determine whether a single versus two-dose BNT162b2 primary vaccination regimen in children 5 to 11 years old with prior SARS-CoV-2 infection was non-inferior in terms of immunogenicity and superior in terms of safety and reactogenicity.

METHODS

Participants were randomly assigned (1:1) to receive either one or two doses, spaced 3 to 12-weeks. The primary endpoint was geometric mean ratio (GMR) of neutralizing antibodies against wild-type SARS-CoV-2 at 28 days post-vaccination with non-inferiority margin defined as a 1.5-fold change in geometric mean titers (GMT). Secondary endpoints included safety and reactogenicity profile and immunogenicity up to 12 months against wild-type and Variants of Concern (VOCs).

RESULTS

In total 31 participants from 3 European countries (median age 9, IQR7-10) were enrolled from May 2022 to January 2024, when the trial was prematurely terminated due to declining interest in COVID-19 vaccination among age-eligible children. Of these, 15 received two doses, and 16 received one. At day 28, GMT of neutralizing antibodies against wild-type SARS-CoV-2 was 1801.1 IU/mL(95%CI:1357.9-2388.9) in the two-dose arm and 1715.5 IU/mL(95%CI:1064.2-2765.4) in the single-dose arm. However, the non-inferiority of the single-dose could not be demonstrated (GMR:0.9; 95%CI:0.5-1.6). Titers remained above 100 IU/mL in both groups at 6 and 12 months. Both schedules elicited high anti-RBD IgG titers against wild-type and neutralizing titers against BA.5 variant at day 28. Eight participants (53%) in the two-dose arm and five (31%) in the single-dose reported a systemic adverse event grade ≥ 2 (P = 0.18) within 7 days of vaccination.

CONCLUSIONS

Both regimens induced robust and sustained immune responses consistent with the possibility that, in children with prior infection, a single dose functions immunologically as a booster of the humoral response. However, the premature termination renders the primary non-inferiority comparison statistically underpowered. The vaccine was well tolerated in both groups. EudraCT registration: 2021-005043-71.

MeSH

Sars-Cov-2, Safety, Vaccines, Antibodies, Rna, Messenger, Antibodies, Neutralizing, Vaccination, Covid-19, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections, Child