Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy

Ashley L St John,Hae Woong Choi,Bruce Blough,Cynthia M Kuhn,Q David Walker,Soman N Abraham,Herman F Staats

doi:10.1038/s41541-020-0161-1

Abstract

Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, mastoparan-7 (M7), to achieve optimal IgA antibody responses in mucosal secretions and effective induction of humoral immunity using a short immunization protocol. This formulation, using a hapten-carrier system to deliver cocaine as antigen, also reduced cocaine penetration of the blood brain barrier and protected mice from its psychoactive effects by reducing cocaine-induced locomotion. Surprisingly, the magnitude of cocaine-specific antibody titers induced by each adjuvant was not the major determinant of functional protection from cocaine challenge. A side-by-side comparison of the two haptens, cocaine and its analog GNC demonstrated that cocaine haptenation resulted in superior functional protection when used in combination with the novel mucosal adjuvant, M7. These results provide a new potential strategy for combatting cocaine addiction through mucosal vaccination.

Highlights

Cocaine is a powerful psychostimulant, the illicit abuse of which has become a serious social and public health concern
Despite the obvious health risks associated with cocaine abuse, >95% of all cocaine addicts who try to quit fail[4] and, notwithstanding our wealth of knowledge regarding the basic science of cocaine chemistry and the biology of cocaine addiction, no successful pharmacotherapies have been generated to combat its addictive properties
We have previously reported that small molecule mast cell (MC) activators are extremely effective mucosal adjuvants.[15]

Summary

Introduction

Cocaine is a powerful psychostimulant, the illicit abuse of which has become a serious social and public health concern. It is estimated that over 14% of Americans aged 12 or older are currently using or have tried cocaine.[1] Cocaine rapidly enters the brain by crossing the blood brain barrier and exerts its effects upon the central nervous system (CNS). This can occur either through the circulation after injection or through direct transport from the nasal cavity to the brain via the olfactory system when inhaled.[2] Cocaine blocks the re-uptake of catecholamines, including dopamine, norepinephrine, and serotonin. Despite the obvious health risks associated with cocaine abuse, >95% of all cocaine addicts who try to quit fail[4] and, notwithstanding our wealth of knowledge regarding the basic science of cocaine chemistry and the biology of cocaine addiction, no successful pharmacotherapies have been generated to combat its addictive properties

Methods

Results

Conclusion