{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:42Z","timestamp":1787026602456,"version":"build-2736575974"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A whole blood stimulation assay was used to investigate\n                      <jats:italic>in vitro<\/jats:italic>\n                      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\u00a0+\u00a028). Samples from eight children were analysed six months after BNT162b2 vaccination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At V2\u00a0+\u00a028, interferon-\u03b3 and monocyte chemoattractant protein-1 responses to\n                      <jats:italic>S. aureus<\/jats:italic>\n                      ,\n                      <jats:italic>E. coli<\/jats:italic>\n                      ,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>monocytogenes<\/jats:italic>\n                      , BCG vaccine,\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      , 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\u00a0+\u00a028 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\u00a0+\u00a028 and cytokine responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1242380","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T13:58:20Z","timestamp":1692971900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists"],"prefix":"10.3389","volume":"14","author":[{"given":"Andr\u00e9s","family":"No\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh D.","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Axelrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Burrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susie","family":"Germano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Burgner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten P.","family":"Perrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Messina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy207","article-title":"Does BCG vaccination protect against nontuberculous mycobacterial infection? 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