TGF-β2 interfering oligonucleotides used as adjuvants for microbial vaccines.

Abstract:

: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.

journal_name

J Leukoc Biol

authors

Tu L,Sun X,Yang L,Zhang T,Zhang X,Li X,Dong B,Liu Y,Yang M,Wang L,Yu Y

doi

10.1002/JLB.5A0420-491R

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

1673-1692

issue

5

eissn

0741-5400

issn

1938-3673

journal_volume

108

pub_type

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