title: Oil-in-Water Emulsion MF59 Increases Germinal Center B Cell Differentiation and Persistence in Response to Vaccination.
abstract: Induction of persistent protective immune responses is a key attribute of a successful vaccine formulation. MF59 adjuvant, an oil-in-water emulsion used in human vaccines, is known to induce persistent high-affinity functional Ab titers and memory B cells, but how it really shapes the Ag-specific B cell compartment is poorly documented. In this study, we characterized the Ab- and Ag-specific B cell compartment in wild-type mice immunized with HlaH35L, a Staphylococcus aureus Ag known to induce measurable functional Ab responses, formulated with MF59 or aluminum salts, focusing on germinal centers (GC) in secondary lymphoid organs. Taking advantage of single-cell flow cytometry analyses, HlaH35L-specific B cells were characterized for the expression of CD38 and GL-7, markers of memory and GC, respectively, and for CD80 and CD73 activation markers. We demonstrated that immunization with MF59-, but not aluminum salt-adjuvanted HlaH35L, induced expanded Ag-specific CD73(+)CD80(-) GC B cells in proximal- and distal-draining lymph nodes, and promoted the persistence of GC B cells, detected up to 4 mo after immunization. In addition to increasing GC B cells, MF59-adjuvanted HlaH35L also increased the frequency of T follicular helper cells. This work extends previous knowledge regarding adaptive immune responses to MF59-adjuvanted vaccines, and, to our knowledge, for the first time an adjuvant used in human licensed products is shown to promote strong and persistent Ag-specific GC responses that might benefit the rational design of new vaccination strategies.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and Dipartimento di Biologia e Biotecnologie "Charles Darwin," Università degli Studi di Roma "La Sapienza," 00185 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lofano
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Giulia
authors.initials: G
authors.lastname: Salvatore
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cantisani
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Monaci
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Corrado
authors.initials: C
authors.lastname: Carrisi
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Simona
authors.initials: S
authors.lastname: Tavarini
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sammicheli
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi Paccani
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Soldaini
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Donatello
authors.initials: D
authors.lastname: Laera
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Oretta
authors.initials: O
authors.lastname: Finco
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagnoli
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy; and sylvie.c.bertholet-girardin@gsk.com.
authors.forename: Sylvie
authors.identifier: http://orcid.org/0000-0002-1298-8859
authors.initials: S
authors.lastname: Bertholet
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology; D002454:Cell Differentiation; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010641:Phenotype; D011136:Polysorbates; D013185:Squalene / Q000276:immunology; D013209:Staphylococcal Vaccines; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D015703:Antigens, CD; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C089950:MF59 oil emulsion; D011136:Polysorbates; D013209:Staphylococcal Vaccines; C021091:staphylococcal alpha-toxin; D013185:Squalene