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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
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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 

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