Reduced durability of hybrid immunity to SARS-CoV-2 in immunocompromised children

Front Immunol. 2024 Dec 17:15:1502598. doi: 10.3389/fimmu.2024.1502598. eCollection 2024.

Abstract

Background: In endemic COVID-19, immunocompromised children are vulnerable until vaccinated but the optimal primary vaccination regime and need for booster doses remains uncertain.

Methods: We recruited 19 immunocompromised children (post-solid organ transplantation, have autoimmune disease or were on current or recent chemotherapy for acute lymphoblastic leukemia), and followed them from the start of primary vaccination with BNT162b2 mRNA SARS-CoV-2 until 1-year post-vaccination. We investigated the quality of vaccine immunogenicity, and longevity of hybrid immunity, in comparison to healthy children.

Results: Immunocompromised children failed to produce T cell and memory B cell (MBC) responses reaching thresholds of protection after 2 doses; a third dose however improved both responses. Initially robust hybrid immunity demonstrated significantly more decline in T cell and MBC responses in immunocompromised compared to healthy children, to levels below the protective threshold by month 12.

Discussion: Immunocompromised children may benefit from a 3-dose primary vaccination regime, with yearly or twice-yearly booster doses for sustained immunity.

Keywords: COVID-19; T cells; adaptive immunity; correlates of protection; memory B cells; vaccine durability; vaccine immunogenicity.

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • BNT162 Vaccine* / administration & dosage
  • BNT162 Vaccine* / immunology
  • COVID-19 Vaccines / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunocompromised Host*
  • Immunogenicity, Vaccine
  • Male
  • Memory B Cells / immunology
  • SARS-CoV-2* / immunology
  • T-Lymphocytes / immunology
  • Vaccination

Substances

  • BNT162 Vaccine
  • Antibodies, Viral
  • COVID-19 Vaccines

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. ET is supported by the National Medical Research Council (NMRC) Clinician-Scientist Award (CSA) (MOH-001415), CT is supported by the NMRC Open Fund – Large Collaborative Grant (OFLCG19May-0034), National University of Singapore Startup Grant (NUHSRO/2023/018/Startup/10) and MOH-PREPARE-CS1-2023-011, and EO is supported by the NMRC Singapore Translational Research (STaR) Award (MOH-001271-00). This study was supported by ET’s NUS award (NUHSRO/2021/081/NUS Med/07/MARVELS) from the Yong Loo Lin School of Medicine, National University of Singapore.