Preclinical efficacy of an anti‐methamphetamine vaccine using E6020 adjuvant

Abstract

Methamphetamine (MA) substance use disorder (SUD) does not have an efficacious pharmacotherapy. We developed a MA vaccine and investigated its potential to attenuate MA induced responses. We examined a novel adjuvant, E6020, a Toll-like receptor-4 (TLR-4) agonist combined with tetanus-toxoid conjugated to succinyl-methamphetamine (TT-SMA) adsorbed on aluminum hydroxide (alum). Adult BALB/c female mice received the vaccine and booster injections at weeks 0, 3, and 6. The efficacy of the vaccine was assessed by the level and affinity of anti-MA antibodies elicited, its ability to attenuate MA induced locomotor activation and its reduction in the amount of MA entering the brains of vaccinated mice. The TT-SMA vaccine containing alum and E6020 adjuvant produced anti-MA antibodies with nanomolar affinities and showed threefold greater peak titer levels than without E6020 (700 vs 250 μg/ml). These antibodies significantly decreased MA-induced locomotor activation (p < .05), and reduced the brain (p < .005) MA levels following MA administration in actively immunized mice. Thus, this anti-MA vaccine formulated with E6020 demonstrated effective functional protection against behavioral disruptions induced by MA. Together, anti-MA vaccine showing a promising improvement in the efficacy of the vaccine that could be an effective candidate vaccine for methamphetamine use disorder (MUD). Furthermore, combinations of adjuvants may be a tool to design vaccines for MA dependence in humans. (Am J Addict 2019;XX:1-8).