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Gel Phase 1,2-Distearoyl-sn-glycero-3-phosphocholine-Based Liposomes Are Superior to Fluid Phase Liposomes at Augmenting Both Antigen Presentation on Major Histocompatibility Complex Class II and Costimulatory Molecule Display by Dendritic Cells in Vitro

Journal article
Authors K. Norling
Valentina Bernasconi
V. A. Hernandez
N. M. Parveen
K. Edwards
Nils Y Lycke
F. Hook
M. Bally
Published in ACS Infectious Diseases
Volume 5
Issue 11
Pages 1867-1878
ISSN 2373-8227
Publication year 2019
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 1867-1878
Language en
Links dx.doi.org/10.1021/acsinfecdis.9b00...
Keywords lipid nanoparticle, adjuvant effect, dendritic cell activation, immunogenicity, antigen delivery, mucosal vaccination, mhc class-ii, interbilayer transfer, immune-responses, fusion protein, vaccine, cd4, ubiquitination, cholesterol, adjuvants, receptor, Pharmacology & Pharmacy, Infectious Diseases
Subject categories Infectious Medicine, Pharmacology

Abstract

Lipid-based nanoparticles have in recent years attracted increasing attention as pharmaceutical carriers. In particular, reports of them having inherent adjuvant properties combined with their ability to protect antigen from degradation make them suitable as vaccine vectors. However, the physicochemical profile of an ideal nanoparticle for vaccine delivery is still poorly defined. Here, we used an in vitro dendritic cell assay to assess the immunogenicity of a variety of liposome formulations as vaccine carriers and adjuvants. Using flow cytometry, we investigated liposome-assisted antigen presentation as well as the expression of relevant costimulatory molecules on the cell surface. Cytokine secretion was further evaluated with an enzyme-linked immunosorbent assay (ELISA). We show that liposomes can successfully enhance antigen presentation and maturation of dendritic cells, as compared to vaccine fusion protein (CTA1-3E alpha-DD) administered alone. In particular, the lipid phase state of the membrane was found to greatly influence the vaccine antigen processing by dendritic cells. As compared to their fluid phase counterparts, gel phase liposomes were more efficient at improving antigen presentation. They were also superior at upregulating the costimulatory molecules CD80 and CD86 as well as increasing the release of the cytokines IL-6 and IL-1 beta. Taken together, we demonstrate that gel phase liposomes, while nonimmunogenic on their own, significantly enhance the antigen-presenting ability of dendritic cells and appear to be a promising way forward to improve vaccine immunogenicity.

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