• Giuseppe Lofano, Francesca Mancini, Giulia Salvatore, Rocco Cantisani, Elisabetta Monaci, Corrado Carrisi, Simona Tavarini, Chiara Sammicheli, Silvia Rossi Paccani, Elisabetta Soldaini, Donatello Laera, Oretta Finco, Sandra Nuti, Rino Rappuoli, Ennio De Gregorio, Fabio Bagnoli, and Sylvie Bertholet.
• 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.
• J. Immunol. 2015 Aug 15; 195 (4): 1617-27.

AbstractInduction 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. Copyright © 2015 by The American Association of Immunologists, Inc.

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