Vaccine Adjuvant MF59 Promotes Retention of Unprocessed Antigen in Lymph Node Macrophage Compartments and Follicular Dendritic Cells

Abstract

Ag retention within lymph nodes (LNs) upon vaccination is critical for the development of adaptive immune responses, because it facilitates the encounter of the Ag with cognate lymphocytes. During a secondary exposure of the immune system to an Ag, immune complexes (ICs) that contain the unprocessed Ag are captured by subcapsular sinus macrophages and are transferred onto follicular dendritic cells, where they persist for weeks, facilitating Ag presentation to cognate memory B cells. The impact of adjuvants on Ag retention within the draining LNs is unknown. In this article, we provide the first evidence, to our knowledge, that the oil-in-water emulsion adjuvant MF59 localizes in subcapsular sinus and medullary macrophage compartments of mouse draining LNs, where it persists for at least 2 wk. In addition, we demonstrate that MF59 promotes accumulation of the unprocessed Ag within these LN compartments and facilitates the consequent deposition of the IC-trapped Ag onto activated follicular dendritic cells. These findings correlate with the ability of MF59 to boost germinal center generation and Ag-specific Ab titers. Our data suggest that the adjuvant effect of MF59 is, at least in part, due to an enhancement of IC-bound Ag retention within the LN and offer insights to improve the efficacy of new vaccine adjuvants.

Carrier priming effect of CRM 197 is related to an enhanced B and T cell activation in meningococcal serogroup A conjugate vaccination. Immunological comparison between CRM 197 and diphtheria toxoid

“…As expected, a co-localization of DT-A568 and FDCs signals was observed in case of pre-existing anti-DT immunity, indicating FDCs capture of the antibody-conjugate immune-complexes. Our observations were consistent with the described LN trafficking of immune complexes [23,30,[36][37][38]. Following the hypothesis of favored anti-carrier B response due to presentation of antibody-conjugate complexes [16], we may speculate that anti-DT antibodies can capture DT based conjugates inducing carrier-specific B cell expansion and detriment of anti-carbohydrate B cell responses.…”

“…Inguinal LNs cryosections and confocal microscopy analyses were executed as reported [30] (details in SI). Staining mix with antibodies conjugated with fluorescent reporters was used: anti-CD21/35-APC (Biolegend) to identify FDCs; anti-CD169-FITC (Serotec) to identify SCS macrophages; anti-F4/80-PB to identify medullary macrophages (MMs).…”

A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses

“…The oil-in-water emulsion adjuvant MF59 can persist in DLNs, promoting accumulation of the unprocessed Ag. Ag retention within lymph nodes is critical for the development of adaptive immune responses, because it facilitates the encounter of the Ag with cognate lymphocytes (40).…”

Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine hemophilia A

“…Indeed, the MF59 preparation of the vaccine has been previously shown to provide antigen retention in the LN and induce lymphocyte recruitment. 30,31 In contrast, the intravenous infusion of FVIII likely elicits immunity in the spleen. 22 We hypothesized that concurrent vaccination and exposure to FVIII attracts immune cells toward the site of vaccination and thus decreases the effective immune response against FVIII.…”