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Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant

[Image: see text] Adjuvants are components of vaccine that enhance the specific immune response against co-inoculated antigens. Recently, we reported the characterization of a synthetic sulfolipid named Sulfavant A (1) as a promising candidate of a novel class of molecular adjuvants based on the sul...

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Autores principales: Manzo, Emiliano, Gallo, Carmela, Fioretto, Laura, Nuzzo, Genoveffa, Barra, Giusi, Pagano, Dario, Krauss, Irene Russo, Paduano, Luigi, Ziaco, Marcello, DellaGreca, Marina, De Palma, Raffaele, Fontana, Angelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711358/
https://www.ncbi.nlm.nih.gov/pubmed/31459869
http://dx.doi.org/10.1021/acsomega.8b03304
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author Manzo, Emiliano
Gallo, Carmela
Fioretto, Laura
Nuzzo, Genoveffa
Barra, Giusi
Pagano, Dario
Krauss, Irene Russo
Paduano, Luigi
Ziaco, Marcello
DellaGreca, Marina
De Palma, Raffaele
Fontana, Angelo
author_facet Manzo, Emiliano
Gallo, Carmela
Fioretto, Laura
Nuzzo, Genoveffa
Barra, Giusi
Pagano, Dario
Krauss, Irene Russo
Paduano, Luigi
Ziaco, Marcello
DellaGreca, Marina
De Palma, Raffaele
Fontana, Angelo
author_sort Manzo, Emiliano
collection PubMed
description [Image: see text] Adjuvants are components of vaccine that enhance the specific immune response against co-inoculated antigens. Recently, we reported the characterization of a synthetic sulfolipid named Sulfavant A (1) as a promising candidate of a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. Here, we report an improved synthesis of the sulfolipid scaffold, as well as the preparation of two analogs named Sulfavant-S (2) and Sulfavant-R (3) with enhanced property to modulate master immune targets such as human dendritic cells (DCs). According to the present approach, synthesis of 1 is reduced from 14 to 11 steps with nearly triplication of the overall yield (11%). The new members 2 and 3 elicit DC maturation at a concentration of 10 nM, which is 1000 times more potent than the parent molecule 1. Analysis of dynamic light scattering indicates self-assembly of Sulfavants and formation of colloidal particles with a small hydrodynamic radius (50 nm) for the epimers 2 and 3 and a larger radius (150 nm) for 1. The colloidal aggregates are responsible for the bell-shaped dose–response curve of these products. We conclude that the particle size also affects the equilibrium with free monomers, thus determining the effective concentration of the sulfolipid molecule at the cellular targets and the different immunological efficacy of 1–3. Sulfavants (1–3) do not show in vitro cytotoxicity at concentrations 10(5) higher than the dose that triggers maximal immune response, thus predicting a low level of toxicological risk in their formulation in vaccines.
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spelling pubmed-67113582019-08-27 Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant Manzo, Emiliano Gallo, Carmela Fioretto, Laura Nuzzo, Genoveffa Barra, Giusi Pagano, Dario Krauss, Irene Russo Paduano, Luigi Ziaco, Marcello DellaGreca, Marina De Palma, Raffaele Fontana, Angelo ACS Omega [Image: see text] Adjuvants are components of vaccine that enhance the specific immune response against co-inoculated antigens. Recently, we reported the characterization of a synthetic sulfolipid named Sulfavant A (1) as a promising candidate of a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. Here, we report an improved synthesis of the sulfolipid scaffold, as well as the preparation of two analogs named Sulfavant-S (2) and Sulfavant-R (3) with enhanced property to modulate master immune targets such as human dendritic cells (DCs). According to the present approach, synthesis of 1 is reduced from 14 to 11 steps with nearly triplication of the overall yield (11%). The new members 2 and 3 elicit DC maturation at a concentration of 10 nM, which is 1000 times more potent than the parent molecule 1. Analysis of dynamic light scattering indicates self-assembly of Sulfavants and formation of colloidal particles with a small hydrodynamic radius (50 nm) for the epimers 2 and 3 and a larger radius (150 nm) for 1. The colloidal aggregates are responsible for the bell-shaped dose–response curve of these products. We conclude that the particle size also affects the equilibrium with free monomers, thus determining the effective concentration of the sulfolipid molecule at the cellular targets and the different immunological efficacy of 1–3. Sulfavants (1–3) do not show in vitro cytotoxicity at concentrations 10(5) higher than the dose that triggers maximal immune response, thus predicting a low level of toxicological risk in their formulation in vaccines. American Chemical Society 2019-04-30 /pmc/articles/PMC6711358/ /pubmed/31459869 http://dx.doi.org/10.1021/acsomega.8b03304 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Manzo, Emiliano
Gallo, Carmela
Fioretto, Laura
Nuzzo, Genoveffa
Barra, Giusi
Pagano, Dario
Krauss, Irene Russo
Paduano, Luigi
Ziaco, Marcello
DellaGreca, Marina
De Palma, Raffaele
Fontana, Angelo
Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant
title Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant
title_full Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant
title_fullStr Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant
title_full_unstemmed Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant
title_short Diasteroselective Colloidal Self-Assembly Affects the Immunological Response of the Molecular Adjuvant Sulfavant
title_sort diasteroselective colloidal self-assembly affects the immunological response of the molecular adjuvant sulfavant
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711358/
https://www.ncbi.nlm.nih.gov/pubmed/31459869
http://dx.doi.org/10.1021/acsomega.8b03304
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