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

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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
BioMed Central
BMC Immunology, 16(1):71
Oral adjuvantRANKLM cellsL. lactisMucosal immunization
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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.

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.

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.
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