A chemically contiguous hapten approach for a heroin-fentanyl vaccine.

Yoshihiro Natori,Lauren C Smith,Candy S Hwang,Kim D Janda,Lucy Lin,Bin Zhou

doi:10.3762/bjoc.15.100

Yoshihiro Natori, Lauren C Smith + Show 4 more

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https://doi.org/10.3762/bjoc.15.100

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Abstract

Background: Increased death due to the opioid epidemic in the United States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks. The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin.Results: We evaluated a series of nine vaccines developed from chemically contiguous haptens composed of both heroin- and fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark heroin vaccine, but exhibited attenuated protection against fentanyl compared to our fentanyl vaccine.Conclusion: After thorough investigation of this strategy, we have identified key considerations for the development of a chemically contiguous heroin–fentanyl vaccine. Importantly, this is the first report of such a strategy in the opioid–drug–vaccine field.

Highlights

In 2016, the Centers for Disease Control (CDC) estimated that approximately 20.4% of the U.S population (e.g., 50 million people) was suffering from chronic pain [1]
As a starting point for our exploration of chemically contiguous drug–hapten conjugates, we envisioned generating a series of structurally diverse heroin–fentanyl haptens with a focus on linker placement and bond distance between each drug’s chemical connections in order to probe the effect of the drug-epitope structure on eliciting an immune response
To facilitate the preparation of a singular hapten that preserves the structure of each parent drug, the heroin- and fentanyl-like haptens were chemically joined by a series of what we hoped to be silent spacers

Summary

Introduction

In 2016, the Centers for Disease Control (CDC) estimated that approximately 20.4% of the U.S population (e.g., 50 million people) was suffering from chronic pain [1]. The overall rate of opioid prescription has declined in the past few years, heroin has become an increasingly common substitute for prescription opioids due to the accessibility and inexpensiveness of the illicit drug This upsurge is attributed to an increase in illicitly manufactured fentanyl, a powerful synthetic opioid commonly used for treatment of pain in cancer and postoperative patients (CDC). The recent emergence of fentanyl resulted in a 264% increase in synthetic opioid deaths within the U.S from 2012 to 2015, due to the fact that users are often unaware of the presence of fentanyl contaminating the supply of heroin and cocaine to enhance their overall potencies This trend is disconcerting due to the observation that the combinatorial consumption of 10% fentanyl in heroin significantly enhances the risk of overdose by prolonging the detrimental effects of respiratory depression and brain hypoxia [2]. The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin

Results

Discussion

Conclusion