AUTHOR=Noé Andrés , Dang Thanh D. , Axelrad Christine , Burrell Emma , Germano Susie , Elia Sonja , Burgner David , Perrett Kirsten P. , Curtis Nigel , Messina Nicole L. 

TITLE=BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1242380

DOI=10.3389/fimmu.2023.1242380

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Vaccines can have beneficial off-target (heterologous) effects that alter immune responses to, and protect against, unrelated infections. The heterologous effects of COVID-19 vaccines have not been investigated in children.</p></sec><sec><title>Aim</title><p>To investigate heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children.</p></sec><sec><title>Methods</title><p>A whole blood stimulation assay was used to investigate <italic>in vitro</italic> cytokine responses to heterologous stimulants (killed pathogens, Toll-like receptor ligands) and SARS-CoV-2 antigens. Samples from 29 children, aged 5-11 years, before and 28 days after a second BNT162b2 vaccination were analysed (V2 + 28). Samples from eight children were analysed six months after BNT162b2 vaccination.</p></sec><sec><title>Results</title><p>At V2 + 28, interferon-γ and monocyte chemoattractant protein-1 responses to <italic>S. aureus</italic>, <italic>E. coli</italic>, <italic>L</italic>. <italic>monocytogenes</italic>, BCG vaccine, <italic>H. influenzae</italic>, hepatitis B antigen, poly(I:C) and R848 stimulations were decreased compared to pre-vaccination. For most of these heterologous stimulants, IL-6, IL-15 and IL-17 responses were also decreased. There were sustained decreases in cytokine responses to viral, but not bacterial, stimulants six months after BNT162b2 vaccination. Cytokine responses to irradiated SARS-CoV-2, and spike glycoprotein subunits (S1 and S2) were increased at V2 + 28 for most cytokines and remained higher than pre-vaccination responses 6 months after BNT162b2 vaccination for irradiated SARS-CoV-2 and S1. There was no correlation between BNT162b2 vaccination-induced anti-SARS-CoV2-receptor binding domain IgG antibody titre at V2 + 28 and cytokine responses.</p></sec><sec><title>Conclusions</title><p>BNT162b2 vaccination in children alters cytokine responses to heterologous stimulants, particularly one month after vaccination. This study is the first to report the immunological heterologous effects of COVID-19 vaccination in children.</p></sec>