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Soluble RANKL expression in Lactococcus lactis and investigation of its potential as an oral vaccine adjuvant

Cited 5 time in Web of Science Cited 8 time in Scopus
Authors
Kim, Jeong-In; Park, Tae-Eun; Maharjan, Sushila; Li, Hui-Shan; Lee, Ho-Bin; Kim, In-Seon; Piao, Dachuan; Lee, Jun-Yeong; Cho, Chong-Su; Bok, Jin-Duck; Hong, Zhong-Shan; Kang, Sang-Kee; Choi, Yun-Jaie
Issue Date
2015-11-25
Publisher
BioMed Central
Citation
BMC Immunology, 16(1):71
Keywords
Oral adjuvantRANKLM cellsL. lactisMucosal immunization
Description
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Abstract
Background
To initiate mucosal immune responses, antigens in the intestinal lumen must be transported into gut-associated lymphoid tissue through M cells. Recently, it has been increasingly recognized that receptor activator of NF-kB ligand (RANKL) controls M cell differentiation by interacting with RANK expressed on the sub-epithelium of Peyers patches. In this study, we increased the number of M cells using soluble RANKL (sRANKL) as a potent mucosal adjuvant.

Results
For efficient oral delivery of sRANKL, we constructed recombinant Lactococcus lactis (L. lactis) IL1403 secreting sRANKL (sRANKL-LAB). The biological activity of recombinant sRANKL was confirmed by observing RANK-RANKL signaling in vitro. M cell development in response to oral administration of recombinant L. lactis was determined by 1.51-fold higher immunohistochemical expression of M cell marker GP-2, compared to that of non-treatment group. In addition, an adjuvant effect of sRANKL was examined by immunization of mice with M-BmpB as a model antigen after treatment with sRANKL-LAB. Compared with the wild-type L. lactis group, the sRANKL-LAB group showed significantly increased systemic and mucosal immune responses specific to M-BmpB.

Conclusions
Our results show that the M cell development by sRANKL-LAB can increase the antigen transcytotic capability of follicle-associated epithelium, and thereby enhance the mucosal immune response, which implies that oral administration of sRANKL is a promising adjuvant strategy for efficient oral vaccination.
Language
English
URI
https://hdl.handle.net/10371/100546
DOI
https://doi.org/10.1186/s12865-015-0132-x
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College of Agriculture and Life Sciences (농업생명과학대학)Program in Agricultural Biotechnology (협동과정-농업생물공학전공)Journal Papers (저널논문_협동과정-농업생물공학전공)
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