The misuse of and addiction to opioids, including prescription analgesics and street drugs such as heroin and fentanyl, is a serious national crisis affecting public health as well as the country’s social and economic welfare. According to the Centers for Disease Control and Prevention (CDC), in 2017 alone, more than 47,000 Americans died as a result of an opioid overdose. The CDC estimates that the total economic burden of prescription opioid misuse in the United States is $78.5 billion a year, including the costs of healthcare, lost productivity, addiction treatment and criminal justice involvement.
As this crisis grows, health researchers are focusing on potential solutions, and one of the most promising novel treatment approaches is an anti-opioid vaccine. Funded by a $250,000 grant from the National Institutes for Health, a team led by Bryce Chackerian at The University of New Mexico (UNM) Health Sciences Center is conducting an innovative one-year pilot research project to develop vaccines that may represent a therapeutic breakthrough in this area. NAU assistant professor Naomi Lee is collaborating with Chackerian and Katheryn Frietze of UNM on the project.
Several studies have shown that vaccines—traditionally used to combat viruses and bacteria—may be an effective way to blunt the effects of drugs. Just as the HPV (human papillomavirus) vaccine protects against certain HPV infections, an opioid vaccine would trigger a patient’s immune system to generate antibodies to attack opioids. When a patient ingests an opioid, these antibodies would prevent molecules of the drug from crossing the blood-brain barrier in the central nervous system, preventing the patient from getting high.
Because opioid molecules do not naturally produce an immune response, however, they need to be conjugated, or attached, to clinically available carrier proteins in order to trigger an immune response. Similar to the HPV vaccine, the team’s study will investigate the use of bacteriophage virus-like particles (VLPs) as carriers, based on the theory that these artificial protein structures will more effectively produce long-lasting antibodies that require smaller doses of the vaccine. The team hypothesizes that VLPs can be used as a highly immunogenic vaccine platform to elicit rapid, high titer and long-lasting antibody responses to opioids.
“We believe that these are features that are likely required for effective vaccine-based treatment for opioid use disorder,” said Lee.
Pilot designed to set the stage for other NIH funding opportunities
The team aims to identify chemical derivatives of hydrocodone, oxycodone and morphine displayed on the VLP surface that elicit high titer antibodies. Findings from the pilot project will inform decisions for a full research proposal targeted at other funding opportunities at NIH.
“We will make derivatives of opioid drugs that can be chemically conjugated at high density on VLPs derived from Qbeta bacteriophage,” said Lee. “Our vaccines will be assessed for immunogenicity in mice over a range of doses and immunization schedules to assess the titers of antibodies elicited by our vaccines, the longevity of the antibody response and the optimal dosing and immunization schedule to achieve long-lasting and high titer antibodies to the drugs of interest.”
A chemical biologist who joined NAU in 2018, Lee’s background is in peptide chemistry, immunology and vaccinology. In addition to novel vaccine development, her work focuses on improving healthcare for American Indian and Alaska Native populations through health disparities research, STEM education and mentoring. In 2018, Lee received the Professional of the Year award from the American Indian Science and Engineering Society (AISES) for her overall leadership and technical achievement. Lee is a member of the Seneca Nation of Indians and serves as a Captain in the Army National Guard.
Kerry Bennett | Office of the Vice President for Research
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