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C-type lectin receptor agonists elicit functional IL21-expressing Tfh cells and induce primary B cell responses in neonates. | LitMetric

AI Article Synopsis

  • C-type lectin receptor (CLR) agonists, like CAF01, are found to be more effective than Toll-like receptor (TLR) agonists, such as GLA-SE, in boosting immune responses in newborn mice after vaccination.
  • The study revealed that while CAF01 enhances critical immune proteins (IL6, IL21) and promotes T follicular helper (Tfh) cells necessary for effective B cell activation, GLA-SE primarily increases IL10 and favors a Th2 immune response.
  • The findings suggest that CLR-based adjuvants hold great potential for developing vaccines for infants due to their ability to stimulate a robust Tfh response crucial for generating immune memory.

Article Abstract

Introduction: 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.

Methods: Here, we explored the mechanisms accounting for the differences in neonatal adjuvanticity between a CLR-based (CAF01) and a TLR4-based (GLA-SE) adjuvant administered with influenza hemagglutinin (HA) in neonatal mice, by using transcriptomics and systems biology analyses.

Results: 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.

Discussion: 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102809PMC
http://dx.doi.org/10.3389/fimmu.2023.1155200DOI Listing

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