C-type lectin receptor agonists elicit functional IL21-expressing Tfh cells and induce primary B cell responses in neonates.
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Vono M, Mastelic-Gavillet B, Mohr E, Östensson M, Persson J, Olafsdottir TA, Lemeille S, Pejoski D, Hartley O, Christensen D, Andersen P, Didierlaurent AM, Harandi AM, Lambert P, Siegrist C
Front Immunol 14 (-) 1155200 [2023-03-31; online 2023-03-31]
C-type lectin receptor (CLR) agonists emerged as superior inducers of primary B cell responses in early life compared with Toll-like receptor (TLR) agonists, while both types of adjuvants are potent in adults. Here, we explored the mechanisms accounting for the differences in neonatal adjuvanticity between a CLR-based (CAF®01) and a TLR4-based (GLA-SE) adjuvant administered with influenza hemagglutinin (HA) in neonatal mice, by using transcriptomics and systems biology analyses. On day 7 after immunization, HA/CAF01 increased IL6 and IL21 levels in the draining lymph nodes, while HA/GLA-SE increased IL10. CAF01 induced mixed Th1/Th17 neonatal responses while T cell responses induced by GLA-SE had a more pronounced Th2-profile. Only CAF01 induced T follicular helper (Tfh) cells expressing high levels of IL21 similar to levels induced in adult mice, which is essential for germinal center (GC) formation. Accordingly, only CAF01- induced neonatal Tfh cells activated adoptively transferred hen egg lysozyme (HEL)-specific B cells to form HEL+ GC B cells in neonatal mice upon vaccination with HEL-OVA. Collectively, the data show that CLR-based adjuvants are promising neonatal and infant adjuvants due to their ability to harness Tfh responses in early life.
Clinical Genomics Gothenburg [Collaborative]
PubMed 37063899
DOI 10.3389/fimmu.2023.1155200
Crossref 10.3389/fimmu.2023.1155200