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Systemic administration of RANKL overcomes the bottleneck of oral vaccine delivery through microfold cells in ileum. | LitMetric

Systemic administration of RANKL overcomes the bottleneck of oral vaccine delivery through microfold cells in ileum.

Biomaterials

Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address:

Published: April 2016

AI Article Synopsis

  • Successful oral antigen delivery faces challenges from gastrointestinal enzymes and M cell uptake barriers, with M cells being a key hurdle for effective transcytosis to Peyer’s patches.* -
  • The study shows that administering full-length transmembrane RANKL (mRANKL) systemically enhances the development of M cells, leading to increased uptake of fluorescent beads and improved antigen transcytosis.* -
  • Mice treated with mRANKL exhibited strong antibody responses (IgA and IgG) after oral immunization, resulting in higher populations of memory B cells and effector CD4 T cells, highlighting the effectiveness of RANKL in improving oral vaccine responses.*

Article Abstract

A successful delivery of antigen through oral route requires to overcome several barriers, such as enzymatic barrier of gastrointestinal tract and epithelial barrier that constitutes of microfold cells (M cells) for antigen uptake. Although each barrier represents a critical step in determining the final efficiency of antigen delivery, the transcytosis of antigen by M cells in the follicle-associated epithelium (FAE) to Peyer's patches appears to be a major bottleneck. Considering the systemic administration of receptor activator of nuclear factor (NF)-ĸB ligand (RANKL) induces differentiation of receptor activator of nuclear factor (NF)-ĸB (RANK)-expressing enterocytes into M cells, here, we illustrated a promising approach of antigen delivery using full length transmembrane RANKL (mRANKL). The results showed that the intraperitoneal injection of mRANKL increased the population of dendritic cells and macrophages in mesenteric lymph nodes and spleen. Subsequently, systemic administration of mRANKL resulted in significantly higher number of functional GP2(+) M cells leading higher transcytosis of fluorescent beads through them. To corroborate the effect of mRANKL in antigen delivery through M cells, we orally delivered microparticulate antigen to mice treated with mRANKL. Oral immunization induced strong protective IgA and systemic IgG antibody responses against orally delivered antigen in mRANKL-treated mice. The higher antibody responses are attributed to the higher transcytosis of antigens through M cells. Ultimately, the higher memory B cells and effector memory CD4 T cells after oral immunization in RANKL-treated mice confirmed potency of RANKL-mediated antigen delivery. To the best of our knowledge, this is the first study to demonstrate significant induction of mucosal and humoral immune responses to M cell targeted oral vaccines after the systemic administration of RANKL.

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Source
http://dx.doi.org/10.1016/j.biomaterials.2016.01.043DOI Listing

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