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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2019
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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. |
format | Online Article Text |
id | pubmed-6711358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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