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

Autor:	Vono M; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Mastelic-Gavillet B; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Mohr E; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Östensson M; Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden., Persson J; Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden., Olafsdottir TA; Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland., Lemeille S; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Pejoski D; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Hartley O; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Christensen D; Vaccine Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark., Andersen P; Vaccine Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark., Didierlaurent AM; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Harandi AM; Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.; Vaccine Evaluation Center, British Columbia (BC) Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Lambert PH; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Siegrist CA; Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Mar 31; Vol. 14, pp. 1155200. Date of Electronic Publication: 2023 Mar 31 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1155200
Abstrakt:	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. Competing Interests: DC and PA are co-inventors on patent applications covering CAF01. As employees, DC and PA have assigned all rights to Statens Serum Institut, a Danish non-profit governmental institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Vono, Mastelic-Gavillet, Mohr, Östensson, Persson, Olafsdottir, Lemeille, Pejoski, Hartley, Christensen, Andersen, Didierlaurent, Harandi, Lambert and Siegrist.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu