Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-28T01:13:07.805Z Has data issue: false hasContentIssue false
  • English
  • Français

Ultrastructural Visualization of Vaccine Adjuvant Uptake In Vitro and In Vivo

Published online by Cambridge University Press:  30 July 2015

Fabiola Giusti ,
Anja Seubert ,
Rocco Cantisani ,
Marco Tortoli ,
Ugo D’Oro ,
Ilaria Ferlenghi ,
Romano Dallai  and
Diego Piccioli
Fabiola Giusti
Affiliation:
Dipartimento di Scienze della Vita, Università degli Studi di Siena, 53100 Siena, Italy
Anja Seubert
Affiliation:
Novartis Vaccines and Diagnostics (a GSK company), 53100 Siena, Italy
Rocco Cantisani
Affiliation:
Novartis Vaccines and Diagnostics (a GSK company), 53100 Siena, Italy
Marco Tortoli
Affiliation:
Novartis Vaccines and Diagnostics (a GSK company), 53100 Siena, Italy
Ugo D’Oro
Affiliation:
Novartis Vaccines and Diagnostics (a GSK company), 53100 Siena, Italy
Ilaria Ferlenghi
Affiliation:
Novartis Vaccines and Diagnostics (a GSK company), 53100 Siena, Italy
Romano Dallai
Affiliation:
Dipartimento di Scienze della Vita, Università degli Studi di Siena, 53100 Siena, Italy
Diego Piccioli*
Affiliation:
Novartis Vaccines and Diagnostics (a GSK company), 53100 Siena, Italy
*
*Corresponding author. diego.x.piccioli@gsk.com
Get access

Abstract

Adjuvants are substances that enhance adaptive immune responses when formulated in a vaccine. Alum and MF59 are two vaccine adjuvants licensed for human vaccination. Their mode of action has not been completely elucidated. Here we show the first ultrastructural visualization of Alum and MF59 interaction with immune cells in vitro and in vivo. We observed that Alum is engulfed by cells as inclusions of laminae that are detectable within draining lymph nodes. MF59 is instead engulfed by cells in vitro as low-electron-dense lipid-like inclusions that display a vesicle pattern, as confirmed by confocal microscopy using fluorescently labeled MF59. However, lipid-like inclusions with different high- and low-electron-dense content are detected within cells of draining lymph nodes when injecting MF59. As high-electron-dense lipid-like inclusions are also detected upon injection of Alum, our results suggest that the low-electron-dense inclusions are formed by engulfed MF59, whereas the high-electron-dense inclusions are proper lipid inclusions. Thus, we demonstrated that vaccine adjuvants are engulfed as inclusions by lymph node cells and hypothesize that adjuvant treatment may modify lipid metabolism.

Keywords

MF59Alumelectron microscopylymph nodevaccine
Type
Biological Applications and Techniques
Information
Microscopy and Microanalysis , Volume 21 , Issue 4 , August 2015 , pp. 791 - 795
Copyright
© Microscopy Society of America 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Calabro, S., Tortoli, M., Baudner, B.C., Pacitto, A., Cortese, M., O’Hagan, D.T., De Gregorio, E., Seubert, A. & Wack, A. (2011). Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine 29(9), 1812–1823.CrossRefGoogle ScholarPubMed
Cantisani, R., Pezzicoli, A., Cioncada, R., Malzone, C., De Gregorio, E., D’Oro, U. & Piccioli, D. (2015). Vaccine adjuvant MF59 promotes retention of unprocessed antigen in lymph node macrophage compartments and follicular dendritic cells. J Immunol 194(4), 1717–1725.CrossRefGoogle ScholarPubMed
Coffman, R.L., Sher, A. & Seder, R.A. (2010). Vaccine adjuvants: Putting innate immunity to work. Immunity 33(4), 492–503.CrossRefGoogle ScholarPubMed
De Gregorio, E., D’Oro, U. & Wack, A. (2009). Immunology of TLR-independent vaccine adjuvants. Curr Opin Immunol 21(3), 339–345.CrossRefGoogle ScholarPubMed
McKee, A.S., Munks, M.W. & Marrack, P. (2007). How do adjuvants work? Important considerations for new generation adjuvants. Immunity 27(5), 687–690.CrossRefGoogle ScholarPubMed
Oleszycka, E. & Lavelle, E.C. (2014). Immunomodulatory properties of the vaccine adjuvant alum. Curr Opin Immunol 28, 1–5.CrossRefGoogle ScholarPubMed
Rappuoli, R., Mandl, C.W., Black, S. & De Gregorio, E. (2011). Vaccines for the twenty-first century society. Nat Rev Immunol 11(12), 865–872.CrossRefGoogle ScholarPubMed
Tritto, E., Mosca, F. & De Gregorio, E. (2009). Mechanism of action of licensed vaccine adjuvants. Vaccine 27(25–26), 3331–3334.CrossRefGoogle ScholarPubMed