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.

• Authors: Liqun Tu, Xiaomeng Sun, Lei Yang, Tiefeng Zhang, Xian Zhang, Xin Li, Boqi Dong, Ye Liu, Ming Yang, Liying Wang, Yongli Yu
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 108 Issue 5 Pg. 1673-1692 (11 2020) ISSN: 1938-3673 [Electronic] United States
• PMID: 32794350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 Society for Leukocyte Biology.

Chemical References

• Adjuvants, Immunologic
• Antigens, Differentiation
• Oligonucleotides
• TGFB2 protein, human
• Tgfb2 protein, mouse
• Transforming Growth Factor beta2
• Vaccines

Topics

• Adjuvants, Immunologic (genetics, pharmacology)
• Animals
• Antigens, Differentiation (genetics, immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Dogs
• Humans
• Madin Darby Canine Kidney Cells
• Mice
• Oligonucleotides (genetics, pharmacology)
• RAW 264.7 Cells
• Transforming Growth Factor beta2 (antagonists & inhibitors, genetics, immunology)
• U937 Cells
• Vaccination
• Vaccines (genetics, immunology, pharmacology)