Recent advances in the discovery and development of TLR ligands as novel therapeutics for chronic HBV and HIV infections

ABSTRACT

Introduction: Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years.

Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands . A TLR7 agonist is in clinical trials for the treatment of chronic HBV infection while a HBV vaccine using a TLR9 ligand as an adjuvant has proven to be superior to conventional HBV vaccines and has been approved for clinical use. Generally, TLR activation may achieve viral control mainly by promoting adaptive immunity to viral proteins.

Expert opinion: Recent research in this field indicates that TLR ligands could be developed as clinically effective drugs if the obstacles concerning toxicity and application routes are overcome. TLR-mediated promotion of adaptive immunity is a major issue for future studies and will determine the future development of TLR ligands as drugs for immunomodulation.

KEYWORDS:

• Chronic viral infection
• hepatitis B virus (HBV)
• human immunodeficiency virus (HIV)
• interferon (IFN)
• pro-inflammatory cytokines
• Toll-like receptor (TLR)
• adaptive immunity

Article Highlights

• Toll-like receptor (TLR) ligands remain promising candidates for antiviral drugs for the treatment of chronic viral infections.

• A TLR7 agonist is currently being tested in clinical trials for the treatment of chronic HBV infection and may be developed further for clinical use.

• A HBV vaccine using a TLR9 ligand as an adjuvant has proven to be superior to conventional HBV vaccines and has been approved.

• Recent research indicates that a great number of obstacles including potential toxicity and a lack of dose-dependence need to be overcome to make TLR ligands clinically useful.

TLR-mediated promotion of adaptive immunity is an issue to be studied in the future for the establishment of TLR ligands for immunomodulation.

This box summarizes key points contained in the article.

Acknowledgments

We thank Mrs. Delia Cosgrove for editorial assistance.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. One referee declares that they work for 3M, a company working on TLR 7/8 agonists but not for this application.

Additional information

Funding

This work is supported by the National Natural Science Foundation of China [91742114 and 91642118], the National Scientific and Technological Major Project of China [2017ZX10202203] and the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST.