Oil-in-Water Emulsion MF59 Increases Germinal Center B Cell Differentiation and Persistence in Response to Vaccination

J Immunol. 2015 Aug 15;195(4):1617-27. doi: 10.4049/jimmunol.1402604. Epub 2015 Jul 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Bacterial / immunology
  • Antibody Specificity / immunology
  • Antigens, CD / metabolism
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Bacterial Toxins / immunology
  • Cell Differentiation*
  • Chemotaxis, Leukocyte / immunology
  • Female
  • Germinal Center / cytology*
  • Germinal Center / immunology*
  • Hemolysin Proteins / immunology
  • Immunophenotyping
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Phenotype
  • Polysorbates*
  • Squalene* / immunology
  • Staphylococcal Vaccines
  • Vaccination*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antigens, CD
  • Bacterial Toxins
  • Hemolysin Proteins
  • MF59 oil emulsion
  • Polysorbates
  • Staphylococcal Vaccines
  • staphylococcal alpha-toxin
  • Squalene