The CTA1-DD adjuvant strongly potentiates follicular dendritic cell function and germinal center formation, which results in improved neonatal immunization
| Autor: | Johan Mattsson, Valentina Bernasconi, Karin Schön, Anneli Strömberg, Nils Lycke, Sophie Schussek, Inta Gribonika, Ulf Alexander Wenzel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cholera Toxin medicine.medical_treatment Recombinant Fusion Proteins Immunology Gene Expression Complement receptor Antibodies Viral Article Immunophenotyping 03 medical and health sciences Mice Peyer's Patches 0302 clinical medicine Immune system Adjuvants Immunologic T-Lymphocyte Subsets Immunology and Allergy Medicine Animals CXCL13 B-Lymphocytes biology Follicular dendritic cells business.industry Germinal center Germinal Center Vaccination 030104 developmental biology Animals Newborn Influenza Vaccines biology.protein Immunization Lymph Nodes Antibody business Adjuvant Dendritic Cells Follicular 030215 immunology |
| Zdroj: | Mucosal Immunology |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | Vaccination of neonates and young infants is hampered by the relative immaturity of their immune systems and the lack of safe and efficacious vaccine adjuvants. Immaturity of the follicular dendritic cells (FDCs), in particular, appears to play a critical role for the inability to stimulate immune responses. Using the CD21mT/mG mouse model we found that at 7 days of life, FDCs exhibited a mature phenotype only in the Peyer´s patches (PP), but our unique adjuvant, CTA1-DD, effectively matured FDCs also in peripheral lymph nodes following systemic, as well as mucosal immunizations. This was a direct effect of complement receptor 2-binding to the FDC and a CTA1-enzyme-dependent enhancing effect on gene transcription, among which CR2, IL-6, ICAM-1, IL-1β, and CXCL13 encoding genes were upregulated. This way we achieved FDC maturation, increased germinal center B-cell- and Tfh responses, and enhanced specific antibody levels close to adult magnitudes. Oral priming immunization of neonates against influenza infection with CTA1-3M2e-DD effectively promoted anti-M2e-immunity and significantly reduced morbidity against a live virus challenge infection. To the best of our knowledge, this is the first study to demonstrate direct effects of an adjuvant on FDC gene transcriptional functions and the subsequent enhancement of neonatal immune responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink