Preclinical efficacy of an anti-methamphetamine vaccine using E6020 adjuvant
| Autor: | Yan Wu, Frank M. Orson, Lynn D. Hawkins, Colin N. Haile, Reetakshi Arora, Thomas R. Kosten, Therese A. Kosten, Muthu Ramakrishnan |
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| Rok vydání: | 2019 |
| Předmět: |
Agonist
medicine.drug_class medicine.medical_treatment Medicine (miscellaneous) Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacotherapy medicine 030304 developmental biology 0303 health sciences biology Alum business.industry Methamphetamine Psychiatry and Mental health Clinical Psychology Titer chemistry Methamphetamine use biology.protein Antibody business Adjuvant 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | The American Journal on Addictions. 28:119-126 |
| ISSN: | 1055-0496 |
| DOI: | 10.1111/ajad.12867 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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