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Preclinical efficacy of an anti‐methamphetamine vaccine using E6020 adjuvant
Author(s) -
Arora Reetakshi,
Haile Colin N.,
Kosten Therese A.,
Wu Yan,
Ramakrishnan Muthu,
Hawkins Lynn D.,
Orson Frank M.,
Kosten Thomas R.
Publication year - 2019
Publication title -
the american journal on addictions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.997
H-Index - 76
eISSN - 1521-0391
pISSN - 1055-0496
DOI - 10.1111/ajad.12867
Subject(s) - adjuvant , methamphetamine , medicine , toxoid , pharmacology , tetanus , immunology , antibody , immunization , vaccination
Background and Objective 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. Methods 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. Results 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. Conclusions Thus, this anti‐MA vaccine formulated with E6020 demonstrated effective functional protection against behavioral disruptions induced by MA. Scientific Significance 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)