Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5-11 years: a phase 2/3, randomized, active-controlled study

Front Immunol. 2024 Sep 2:15:1445459. doi: 10.3389/fimmu.2024.1445459. eCollection 2024.

Abstract

Background: DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, non-inferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here.

Methods: Children aged 5-11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29.

Results: Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, -7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8-29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off.

Conclusions: Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years.

Clinical trial registration: https://jrct.niph.go.jp/, identifier jRCT2031220665.

Keywords: COVID-19; DS-5670a/b; SARS-CoV-2; booster vaccination; children; non-inferiority; omicron variant.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III

MeSH terms

  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • BNT162 Vaccine / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunization, Secondary*
  • Immunogenicity, Vaccine
  • Male
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / immunology
  • Vaccination / methods

Substances

  • Antibodies, Viral
  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • BNT162 Vaccine
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work to develop and produce a vaccine against SARS-CoV-2 was funded and supported by the Ministry of Health, Labour and Welfare (MHLW) and Japan Agency for Medical Research and Development (AMED) under Grant Number JP21nf0101625, as part of the initiatives to combat COVID-19.