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Antigen-containing liposomes engrafted with flagellin-related peptides are effective vaccines that can induce potent antitumor immunity and immunotherapeutic effect

Abdus Salam Abul, Faham; Altin, Joseph

Description

The bacterial protein flagellin can trigger immune responses to infections by interacting with TLR5 on APCs, and Ag-flagellin fusion proteins can act as effective vaccines. We report that flagellin-related peptides containing a His-tag and sequence related to conserved N-motif (aa 85-111) of FliC flagellin, purportedly involved in the interaction of flagellin with TLR5, can be used to target delivery of liposomal Ag to APCs in vitro and in vivo. When engrafted onto liposomes, two...[Show more]

dc.contributor.authorAbdus Salam Abul, Faham
dc.contributor.authorAltin, Joseph
dc.date.accessioned2015-12-08T22:37:16Z
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/35457
dc.description.abstractThe bacterial protein flagellin can trigger immune responses to infections by interacting with TLR5 on APCs, and Ag-flagellin fusion proteins can act as effective vaccines. We report that flagellin-related peptides containing a His-tag and sequence related to conserved N-motif (aa 85-111) of FliC flagellin, purportedly involved in the interaction of flagellin with TLR5, can be used to target delivery of liposomal Ag to APCs in vitro and in vivo. When engrafted onto liposomes, two flagellin-related peptides, denoted as 9Flg and 42Flg, promoted strong liposome binding to murine bone marrow-derived dendritic cells and CD11c+ splenocytes, and cell binding correlated with expression of TLR5. Liposomes engrafted with 9Flg or 42Flg induced functional MyD88-dependent maturation of dendritic cells in vivo. The vaccination of mice with 9Flg liposomes containing OVA induced OVA-specific T cell priming, increased the number of Ag-responsive IFN-γ-producing CD8+ T cells, and increased Ag-specific IgG1 and IgG2b in serum. Importantly, the vaccination of C57BL/6 mice with syngeneic B16-OVA-derived plasma membrane vesicles, engrafted with 9Flg or 42Flg, potently inhibited tumor growth/metastasis and induced complete tumor regression in the majority of mice challenged with the syngeneic B16-OVA melanoma, in the lung and s.c. tumor models. Strong antitumor responses were also seen in studies using the s.c. P815 tumor model. Therefore, vaccination with Ag-containing liposomes engrafted with 9Flg or 42Flg is a powerful strategy to exploit the innate and adaptive immune systems for the development of potent vaccines and cancer immunotherapies.
dc.publisherAmerican Association of Immunologists
dc.sourceJournal of Immunology
dc.subjectKeywords: antibody; flagellin; gamma interferon; immunoglobulin G2b; liposome; myeloid differentiation factor 88; peptide vaccine; toll like receptor 5; amino acid sequence; animal cell; animal experiment; animal model; animal tissue; antigen presenting cell; artic
dc.titleAntigen-containing liposomes engrafted with flagellin-related peptides are effective vaccines that can induce potent antitumor immunity and immunotherapeutic effect
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume185
dc.date.issued2010
local.identifier.absfor111204 - Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
local.identifier.ariespublicationu8611701xPUB124
local.type.statusPublished Version
local.contributor.affiliationAbdus Salam Abul, Faham, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationAltin, Joseph, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue3
local.bibliographicCitation.startpage1744
local.bibliographicCitation.lastpage1754
local.identifier.doi10.4049/jimmunol.1000027
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
dc.date.updated2016-02-24T11:41:04Z
local.identifier.scopusID2-s2.0-77956408001
local.identifier.thomsonID000280177400051
CollectionsANU Research Publications

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