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

Maria Vono; Beatris Mastelic-Gavillet; Elodie Mohr; Malin Östensson; Josefine Persson; Thorunn A Olafsdottir; Sylvain Lemeille; David Pejoski; Oliver Hartley; Dennis Christensen; Peter Andersen; Arnaud M Didierlaurent; Ali M Harandi; Paul-Henri Lambert; Claire-Anne Siegrist

doi:10.3389/fimmu.2023.1155200

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

Front Immunol. 2023 Mar 31:14:1155200. doi: 10.3389/fimmu.2023.1155200. eCollection 2023.

Authors

Maria Vono¹, Beatris Mastelic-Gavillet¹, Elodie Mohr¹, Malin Östensson², Josefine Persson², Thorunn A Olafsdottir³, Sylvain Lemeille⁴, David Pejoski¹, Oliver Hartley⁴, Dennis Christensen⁵, Peter Andersen⁵, Arnaud M Didierlaurent¹, Ali M Harandi^{2

6}, Paul-Henri Lambert¹, Claire-Anne Siegrist¹

Affiliations

¹ Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
² Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
³ Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland.
⁴ Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
⁵ Vaccine Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
⁶ Vaccine Evaluation Center, British Columbia (BC) Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

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 (CAF^®01) 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.

Keywords: C-type lectin receptor agonists; T follicular helper (Tfh); interleukin-21 (IL-21); interleukin-6 (IL-6); neonatal vaccinology; toll-like receptor agonists; vaccine adjuvants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Animals
Animals, Newborn
B-Lymphocytes*
Germinal Center*
Lectins, C-Type* / agonists
Mice
T Follicular Helper Cells*

Substances

Adjuvants, Immunologic
interleukin-21
Lectins, C-Type

Grants and funding

This work is supported through funding to C-AS and AH from the European Commission of the Seventh Framework Programme (Advanced Immunization Technologies, 280873), and to C-AS from the Swiss National Science Foundation (grant number 310000-111926/1 and 310030-165960).