Assessing Biological, Structural, and Ethical Barriers to Implementation of Opioid Vaccination

Abstract

Given the diverse public health challenges facing the United States today, the opioid overdose epidemic is among the most pressing. Nearly 50,000 individuals died in the past year due to opioid overdose, and around 500,000 individuals have died due to opioid overdose overall. These staggering numbers of deaths have unfortunately occurred despite the availability of effective treatments for both overdose reversal and opioid use disorder. Unfortunately, less than 20% of individuals who may qualify for such treatments actually access them. Given the clear ongoing need for new solutions, vaccination against both prescription and illicit opioids has been proposed as an alternative method to address this crisis. Indeed, following on from promising pre‐clinical work in both rodents and non‐human primates, the first clinical trials to test opioid vaccines have now been registered. Considering that previous vaccines directed against small molecules such as nicotine ultimately failed to reach the market, and that even approved treatments for opioid use disorder face barriers to dissemination and widespread use, we undertook a concerted, human subject investigation into three separate domains of translational barriers that could impact the ultimate success of the opioid vaccine approach. We first investigated biological barriers to success, specifically using ELISA to assess the blood of individuals who were either chronic opioid users or matched controls to look for development of endogenous anti‐opioid antibodies that could ultimately suppress immune responses to vaccination. We next assessed structural barriers to implementation, surveying current and future healthcare providers about present use and perceived structural challenges to the use of interventions for opioid use disorder. Finally, we assessed ethical barriers to implementation of vaccine‐based therapeutics for substance use disorders, also using a targeted survey approach. Overall, this investigation identified limited evidence of endogenous antibody formation in chronic prescription opioid users, identified some structural difficulties arising from injectable formulations and cost concerns, and identified ethical concerns regarding compulsory use of vaccination, as well as potential use in protected classes of individuals. Nevertheless, opioid vaccination was reported to be a helpful potential addition for the treatment of opioid use disorder and overdose.Support or Funding InformationThis work was generously supported by the ALSAM foundation (5‐77693), the UW‐Madison School of Pharmacy, and Office of the Vice Chancellor for Research and Graduate Education. Furthermore, this study was conducted in collaboration with the Pharmacy Practice Enhancement and Action Research Link (PearlRx) of Wisconsin, a statewide pharmacist practice‐based research network which is in part supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR002373 and the Pharmacy Society of Wisconsin. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.Competitive ELISA with Oxycodone demonstrates little difference in serum binding to OXY‐BSA, between chronically opioid exposed and opioid naive subjects with lower‐back pain, indicating that endogenous anti‐opioid antibodies may not be a biological barrier to vaccine success in this population. MEan +/− SEM.Figure 1Currentlly practicing healthcare providers surveyed through PearlRx indicate that affordability is the greatest structural barrier to implementation of anti‐opioid vaccination, while lack of time is the lowest structural barrier. Provider availability, patient refusal, and access to the medication were of intermediate concern. Mean +/− SEM.Figure 2