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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
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2019 (Engelska)Ingår i: ACS Infectious Diseases, ISSN 2373-8227, Vol. 5, nr 11, s. 1867-1878Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
American Chemical Society (ACS), 2019. Vol. 5, nr 11, s. 1867-1878
Nyckelord [en]
lipid nanoparticle, adjuvant effect, dendritic cell activation, immunogenicity, antigen delivery, mucosal vaccination
Nationell ämneskategori
Infektionsmedicin
Identifikatorer
URN: urn:nbn:se:umu:diva-165749DOI: 10.1021/acsinfecdis.9b00189ISI: 000496041000006PubMedID: 31498993OAI: oai:DiVA.org:umu-165749DiVA, id: diva2:1376653
Forskningsfinansiär
Stiftelsen för strategisk forskning (SSF), SB12-0088Vetenskapsrådet, 2018-04900Knut och Alice Wallenbergs StiftelseTillgänglig från: 2019-12-10 Skapad: 2019-12-10 Senast uppdaterad: 2019-12-10Bibliografiskt granskad

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Bally, Marta

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Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)Avdelningen för virologi
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