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Immunol Lett. 2015 Nov;168(1):89-97. doi: 10.1016/j.imlet.2015.09.007. Epub 2015 Sep 14.

New TLR7 agonists with improved humoral and cellular immune responses.

Author information

1
Baylor Institute for Immunology Research, 3434 Live Oak St., Dallas, TX 75204, USA; Baylor University, Institute for Biomedical Studies, One Bear Place #97224, Waco, TX 76798, USA.
2
Baylor University, Department of Chemistry and Biochemistry, One Bear Place #97348, Waco, TX 76798, USA.
3
Baylor Institute for Immunology Research, 3434 Live Oak St., Dallas, TX 75204, USA.
4
Baylor Institute for Immunology Research, 3434 Live Oak St., Dallas, TX 75204, USA; Baylor University, Institute for Biomedical Studies, One Bear Place #97224, Waco, TX 76798, USA; Baylor University, Department of Chemistry and Biochemistry, One Bear Place #97348, Waco, TX 76798, USA.
5
Baylor Institute for Immunology Research, 3434 Live Oak St., Dallas, TX 75204, USA; Baylor University, Institute for Biomedical Studies, One Bear Place #97224, Waco, TX 76798, USA. Electronic address: sangkono@baylorhealth.edu.

Abstract

Toll-like receptor 7 (TLR7) agonists are of interest as vaccine adjuvants and cancer therapeutics. Therefore, development of new TLR7 agonists that can efficiently promote host immune responses without evoking side effects is of great importance. Here, we describe two new compounds, J4 and F4, which elicit intracellular signaling exclusively via TLR7. Interestingly, both J4 and F4 induced less cytokine secretion (IL-1β, IL-6, IL-10, IL-12p40, TNFα, and IL-12p70) from myeloid dendritic cells (mDCs) and monocytes than CL075 and R848; however, they all generated similar levels of phenotype maturation of antigen presenting cells (APCs), including plasmacytoid DCs. We further found that J4- and F4-induced APC activation was largely dependent on the activation of NF-κB and p38. Lastly, J4 and F4 could efficiently promote B cell proliferation and plasmablast differentiation as well as antigen-specific CD8(+) T cell responses in human in vitro. Therefore, these new TLR7 agonists could be employed to facilitate the development of new therapeutics and vaccine adjuvants against cancers and microbial infections.

KEYWORDS:

Adjuvant; Dendritic Cell; TLR7; Vaccine

PMID:
26381186
DOI:
10.1016/j.imlet.2015.09.007
[Indexed for MEDLINE]

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