MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life
| Autor: | Claire-Anne Siegrist, Paul-Henri Lambert, Flora Castellino, Floriane Auderset, Anja Seubert, Beatris Mastelic Gavillet, Giuseppe Del Giudice, John S. Tregoning, Ennio De Gregorio, Christiane S. Eberhardt |
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| Rok vydání: | 2015 |
| Předmět: |
Squalene
medicine.medical_treatment Immunology MF59 Polysorbates Hemagglutinin (influenza) Enzyme-Linked Immunosorbent Assay ddc:616.07 Real-Time Polymerase Chain Reaction Mice 03 medical and health sciences Germinal Center/immunology Influenza A Virus H1N1 Subtype 0302 clinical medicine T-Lymphocytes Helper-Inducer/immunology Adjuvants Immunologic Adjuvants Immunologic/pharmacology Adjuvanticity medicine Squalene/immunology/pharmacology Animals Immunology and Allergy B cell 030304 developmental biology 0303 health sciences ddc:618 biology Effector Polysorbates/pharmacology Germinal center T-Lymphocytes Helper-Inducer Influenza Vaccines/immunology Flow Cytometry Germinal Center Immunohistochemistry 3. Good health medicine.anatomical_structure Influenza A Virus H1N1 Subtype/immunology Animals Newborn Immunization Influenza Vaccines biology.protein Adjuvant 030215 immunology |
| Zdroj: | J Immunol Journal of Immunology, Vol. 194, No 10 (2015) pp. 4836-4845 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1402071 |
| Popis: | The early life influenza disease burden calls for more effective vaccines to protect this vulnerable population. Influenza vaccines including the MF59 oil-in-water adjuvant induce higher, broader, and more persistent Ab responses in adults and particularly in young, through yet undefined mechanisms. In this study, we show that MF59 enhances adult murine IgG responses to influenza hemagglutinin (HA) by promoting a potent T follicular helper cells (TFH) response, which directly controls the magnitude of the germinal center (GC) B cell response. Remarkably, this enhancement of TFH and GC B cells is already fully functional in 3-wk-old infant mice, which were fully protected by HA/MF59 but not HA/PBS immunization against intranasal challenge with the homologous H1N1 (A/California/7/2009) strain. In 1-wk-old neonatal mice, MF59 recruits and activates APCs, efficiently induces CD4+ effector T cells and primes for enhanced infant responses but induces few fully functional TFH cells, which are mostly follicular regulatory T cells, and poor GC and anti-HA responses. The B cell adjuvanticity of MF59 appears to be mediated by the potent induction of TFH cells which directly controls GC responses both in adult and early life, calling for studies assessing its capacity to enhance the efficacy of influenza immunization in young infants. |
| Databáze: | OpenAIRE |
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