PMID- 30701618
OWN - NLM
STAT- MEDLINE
DCOM- 20200131
LR  - 20200131
IS  - 1521-0391 (Electronic)
IS  - 1055-0496 (Linking)
VI  - 28
IP  - 2
DP  - 2019 Feb
TI  - Preclinical efficacy of an anti-methamphetamine vaccine using E6020 adjuvant.
PG  - 119-126
LID - 10.1111/ajad.12867 [doi]
AB  - 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 mug/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).
CI  - (c) 2019 American Academy of Addiction Psychiatry.
FAU - Arora, Reetakshi
AU  - Arora R
AUID- ORCID: 0000-0002-5437-4521
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, Texas.
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
FAU - Haile, Colin N
AU  - Haile CN
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, Texas.
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
AD  - Department of Psychology, University of Houston, Houston, Texas.
FAU - Kosten, Therese A
AU  - Kosten TA
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, Texas.
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
AD  - Department of Psychology, University of Houston, Houston, Texas.
FAU - Wu, Yan
AU  - Wu Y
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, Texas.
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
FAU - Ramakrishnan, Muthu
AU  - Ramakrishnan M
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
AD  - Immunology Allergy & Rheumatology, Department of Medicine, Baylor College of 
      Medicine, Houston, Texas.
FAU - Hawkins, Lynn D
AU  - Hawkins LD
AD  - Eisai AiM Institute, Andover, Massachusetts.
FAU - Orson, Frank M
AU  - Orson FM
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
AD  - Immunology Allergy & Rheumatology, Department of Medicine, Baylor College of 
      Medicine, Houston, Texas.
FAU - Kosten, Thomas R
AU  - Kosten TR
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, Texas.
AD  - The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
LA  - eng
GR  - DP1 DA033502/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190131
PL  - England
TA  - Am J Addict
JT  - The American journal on addictions
JID - 9208821
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Drug Combinations)
RN  - 0 (ER-804053)
RN  - 0 (Phospholipids)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tetanus Toxoid)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (succinyl-methamphetamine-tetanus toxoid vaccine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
SB  - IM
MH  - Adjuvants, Immunologic/pharmacology
MH  - Aluminum Hydroxide/*pharmacology
MH  - Amphetamine-Related Disorders/*therapy
MH  - Animals
MH  - Biological Availability
MH  - Drug Combinations
MH  - Drug Monitoring/methods
MH  - Methamphetamine/*antagonists & inhibitors
MH  - Mice
MH  - Models, Animal
MH  - Phospholipids/*pharmacology
MH  - Tetanus Toxoid/*pharmacology
MH  - Toll-Like Receptor 4/agonists
MH  - Treatment Outcome
EDAT- 2019/02/01 06:00
MHDA- 2020/02/01 06:00
CRDT- 2019/02/01 06:00
PHST- 2018/08/01 00:00 [received]
PHST- 2019/01/02 00:00 [revised]
PHST- 2019/01/12 00:00 [accepted]
PHST- 2019/02/01 06:00 [pubmed]
PHST- 2020/02/01 06:00 [medline]
PHST- 2019/02/01 06:00 [entrez]
AID - 10.1111/ajad.12867 [doi]
PST - ppublish
SO  - Am J Addict. 2019 Feb;28(2):119-126. doi: 10.1111/ajad.12867. Epub 2019 Jan 31.