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TGF‐β2 interfering oligonucleotides used as adjuvants for microbial vaccines
Author(s) -
Tu Liqun,
Sun Xiaomeng,
Yang Lei,
Zhang Tiefeng,
Zhang Xian,
Li Xin,
Dong Boqi,
Liu Ye,
Yang Ming,
Wang Liying,
Yu Yongli
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.5a0420-491r
Subject(s) - biology , immune system , cd80 , cd40 , cd86 , adjuvant , cytotoxic t cell , priming (agriculture) , t cell , immunology , biochemistry , botany , germination , in vitro
The success of using immune checkpoint inhibitors to treat cancers implies that inhibiting an immunosuppressive cytokine, such as TGF‐β2, could be a strategy to develop novel adjuvants for microbial vaccines. To develop nucleic acid based TGF‐β2 inhibitors, we designed three antisense oligonucleotides, designated as TIO1, TIO2, and TIO3, targeting the conserve regions identical in human and mouse TGF‐β2 mRNA 3′‐untranslated region. In cultured immune cells, TIO3 and TIO1 significantly reduced the TGF‐β2 mRNA expression and protein production. In mice, the TIO3 and TIO1, when formulated in various microbial vaccines, significantly enhanced the antibody response to the vaccines, and the TIO3‐adjuvanted influenza virus vaccine induced effective protection against the influenza virus challenge. In the immunized mice, TIO3 formulated in microbial vaccines dramatically reduced surface‐bound TGF‐β2 expression on CD4 + T cells and CD19 + B cells in the lymph node (LN) cells and spleen cells; up‐regulated the expression of CD40, CD80, CD86, and MHC II molecules on CD19 + B cells and CD11c + dendritic cells; and promoted IFN‐γ production in CD4 + T cells and CD8 + T cells in the LN cells. Overall, TIO3 or TIO1 could be used as a novel type of adjuvant for facilitating the microbial vaccines to elicit more vigorous and persistent antibody response by interfering with TGF‐β2 expression.