title: MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life.
abstract: 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.
authors: Department of Pathology-Immunology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland;
authors: Beatris
authors: B
authors: Mastelic Gavillet
authors: Department of Pathology-Immunology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland;
authors: Christiane S
authors: CS
authors: Eberhardt
authors: Department of Pathology-Immunology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland;
authors: Floriane
authors: F
authors: Auderset
authors: Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors: Flora
authors: F
authors: Castellino
authors: Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors: Anja
authors: A
authors: Seubert
authors: Mucosal Infection and Immunity Group, Section of Virology, St. Mary's Campus, Imperial College London, London W2 1PG, United Kingdom.
authors: John S
authors: JS
authors: Tregoning
authors: Department of Pathology-Immunology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland;
authors: Paul-Henri
authors: PH
authors: Lambert
authors: Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors: Ennio
authors: E
authors: de Gregorio
authors: Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors: Giuseppe
authors: G
authors: Del Giudice
authors: Department of Pathology-Immunology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland; Claire-Anne.Siegrist@unige.ch.
authors: Claire-Anne
authors: CA
authors: Siegrist
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D011136:Polysorbates / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013185:Squalene / Q000276:immunology / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene