High-affinity antigen association to cationic liposomes via coiled coil-forming peptides induces a strong antigen-specific CD4


Journal

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778

Informations de publication

Date de publication:
Jan 2021
Historique:
received: 11 08 2020
revised: 05 11 2020
accepted: 08 11 2020
pubmed: 15 11 2020
medline: 21 9 2021
entrez: 14 11 2020
Statut: ppublish

Résumé

Liposomes are widely investigated as vaccine delivery systems, but antigen loading efficiency can be low. Moreover, adsorbed antigen may rapidly desorb under physiological conditions. Encapsulation of antigens overcomes the latter problem but results in significant antigen loss during preparation and purification of the liposomes. Here, we propose an alternative attachment method, based on a complementary heterodimeric coiled coil peptide pair pepK and pepE. PepK was conjugated to cholesterol (yielding CPK) and pepE was covalently linked to model antigen OVA323 (yielding pepE-OVA323). CPK was incorporated in the lipid bilayer of cationic liposomes (180 nm in size). Antigen was associated more efficiently to functionalized liposomes (Kd 166 nM) than to cationic liposomes (Kd not detectable). In vivo co-localization of antigen and liposomes was strongly increased upon CPK-functionalization (35% -> 80%). CPK-functionalized liposomes induced 5-fold stronger CD4

Identifiants

pubmed: 33188929
pii: S0939-6411(20)30328-3
doi: 10.1016/j.ejpb.2020.11.005
pii:
doi:

Substances chimiques

Adjuvants, Immunologic 0
CD4 Antigens 0
Liposomes 0
Peptides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

96-105

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

R J T Leboux (RJT)

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.

N Benne (N)

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.

W L van Os (WL)

Div. of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.

J Bussmann (J)

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.

A Kros (A)

Div. of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.

W Jiskoot (W)

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.

B Slütter (B)

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands. Electronic address: b.a.slutter@lacdr.leidenuniv.nl.

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Classifications MeSH