A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response

Micelles from amphiphilic polylactide-block-poly(<i>N</i>-acryloxysuccinimide-<i>co</i>-<i>N</i>-vinylpyrrolidone) (PLA-b-P(NAS-<i>co</i>-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were...

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Main Authors: Myriam Lamrayah, Capucine Phelip, Céline Coiffier, Céline Lacroix, Thibaut Willemin, Thomas Trimaille, Bernard Verrier
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/1/107
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author Myriam Lamrayah
Capucine Phelip
Céline Coiffier
Céline Lacroix
Thibaut Willemin
Thomas Trimaille
Bernard Verrier
author_facet Myriam Lamrayah
Capucine Phelip
Céline Coiffier
Céline Lacroix
Thibaut Willemin
Thomas Trimaille
Bernard Verrier
author_sort Myriam Lamrayah
collection DOAJ
description Micelles from amphiphilic polylactide-block-poly(<i>N</i>-acryloxysuccinimide-<i>co</i>-<i>N</i>-vinylpyrrolidone) (PLA-b-P(NAS-<i>co</i>-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive <i>N</i>-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.
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spelling doaj.art-b5ed600d0a6a4b909f06d08b0af535882023-11-23T15:04:00ZengMDPI AGPharmaceutics1999-49232022-01-0114110710.3390/pharmaceutics14010107A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune ResponseMyriam Lamrayah0Capucine Phelip1Céline Coiffier2Céline Lacroix3Thibaut Willemin4Thomas Trimaille5Bernard Verrier6Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), Institut de Biologie et Chimie des Protéines (IBCP), CNRS UMR 5305, Université Lyon 1, Université de Lyon, 69367 Lyon, FranceLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), Institut de Biologie et Chimie des Protéines (IBCP), CNRS UMR 5305, Université Lyon 1, Université de Lyon, 69367 Lyon, FranceLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), Institut de Biologie et Chimie des Protéines (IBCP), CNRS UMR 5305, Université Lyon 1, Université de Lyon, 69367 Lyon, FranceLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), Institut de Biologie et Chimie des Protéines (IBCP), CNRS UMR 5305, Université Lyon 1, Université de Lyon, 69367 Lyon, FranceLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), Institut de Biologie et Chimie des Protéines (IBCP), CNRS UMR 5305, Université Lyon 1, Université de Lyon, 69367 Lyon, FranceLaboratoire Ingénierie des Matériaux Polymères (IMP), CNRS UMR 5223, Université Lyon 1, Université de Lyon, 69622 Villeurbanne, FranceLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), Institut de Biologie et Chimie des Protéines (IBCP), CNRS UMR 5305, Université Lyon 1, Université de Lyon, 69367 Lyon, FranceMicelles from amphiphilic polylactide-block-poly(<i>N</i>-acryloxysuccinimide-<i>co</i>-<i>N</i>-vinylpyrrolidone) (PLA-b-P(NAS-<i>co</i>-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive <i>N</i>-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.https://www.mdpi.com/1999-4923/14/1/107micellesvaccine deliveryimmunizationadjuvantsnanoparticlesbiodistribution
spellingShingle Myriam Lamrayah
Capucine Phelip
Céline Coiffier
Céline Lacroix
Thibaut Willemin
Thomas Trimaille
Bernard Verrier
A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
Pharmaceutics
micelles
vaccine delivery
immunization
adjuvants
nanoparticles
biodistribution
title A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
title_full A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
title_fullStr A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
title_full_unstemmed A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
title_short A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
title_sort polylactide based micellar adjuvant improves the intensity and quality of immune response
topic micelles
vaccine delivery
immunization
adjuvants
nanoparticles
biodistribution
url https://www.mdpi.com/1999-4923/14/1/107
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