TLR7/8 Ligands for Use in Opioid Vaccines
Ligands with the potential for preventing fatal overdose of opioid users and protect against or treat Opioid Use Disorder patients
Technology Overview
Building on their work as part of the Precision Vaccines Program, researchers in the Levy lab have developed a method of enhancing immune response to anti-opioid vaccine by using agonists of Toll-like Receptor 7 and 8 (TLR7/8) as adjuvants. Anti-opioid vaccines elicit polyclonal antibodies that selectively bind the target opioid, preventing its crossing the blood brain barrier. Adjuvanted anti-opioid vaccine that achieves high serum antibody concentrations over an extended period can reduce incidence of opioid-related overdoses.
This invention reports a novel molecular approach to shape human immune responses in individuals with a history of OUD using small molecules with in vitro TLR7/8 receptor specific adjuvant activity towards human leukocytes. A novel adjuvant strategy may lead to robust and balanced Th-polarizing cytokine production in whole blood from OUD participants, that may lead to appropriately adjuvanted-opioid vaccines to induce immune responses favorable for enhancing protective immunity in the targeted population.
Figure 1
Further Details:
• Barrientos, Rodell C et al. “Novel Vaccine That Blunts Fentanyl Effects and Sequesters Ultrapotent Fentanyl Analogues.” Molecular pharmaceutics vol. 17,9 (2020): 3447-3460. doi:10.1021/acs.molpharmaceut.0c00497
Stage of Development
Proof of concept.
- Whole blood samples collected from OUD study participants
- Candidate small molecule adjuvants were screened using a cytokine readout
- Lead molecules e.g. TLR7/8 agonists were validated using a mouse immunization model and measurement of anti-FEN antibodies
Benefits
- Adjuvant activity in a distinct immune population with a history of OUD
- Small molecule category amenable to affordable scale up for mass production
- Potentially useful for development of vaccines against other drugs
Applications
- Preventing fatal overdose of opioid users
- Protect against or treat Opioid Use Disorder patients
Patents
IP Status
- Patent application submitted
