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Published on: January 22, 2016
Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular
Colin N Haile1, Kurt J Varner2, Xia Huijing2
1Department of Psychology/TIMES, University of Houston, Houston, TX 77204, USA.
Background:
Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod.
Methods:
Mice were vaccinated (0, 3, 6 weeks) with TT-SMA+alum and various doses of entolimod to determine an optimal dose for enhancing immunogenicity against MA. Functional effects were then assessed using MA-induced locomotor activation in mice. Experiments using passive immunization of antibodies generated by the vaccine tested its ability to attenuate MA-induced cardiovascular effects and alter the reinforcing effects of MA in an MA-induced reinstatement of a drug seeking model of relapse in male and female rats.
Results:
Antibody levels peaked at 10 weeks following vaccination with TT-SMA+alum combined with entolimod (1, 3 and 10 μg). MA-induced locomotor activation was significantly attenuated in vaccinated vs. unvaccinated mice and antibody levels significantly correlated with ambulation levels. Passive immunization decreased mean arterial pressure following MA dosing in rats of both sexes but did not alter heart rate. Passive immunization also attenuated the ability of MA to reinstate extinguished drug-seeking behavior in male and female rats. Results support further development of this vaccine for relapse prevention for individuals with MUD.
Insights
This study developed an anti-methamphetamine (MA) vaccine, combining a tetanus-toxoid conjugate with an immune stimulant. The vaccine successfully reduced MA-induced behaviors in animal models, showing promise for treating methamphetamine use disorder (MUD).
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Methamphetamine use disorder (MUD) presents a significant public health challenge with no approved treatments.
- This research advances vaccine development for MUD, building on prior anti-methamphetamine (MA) vaccine work.
- A novel vaccine formulation combines tetanus-toxoid conjugated to succinyl-methamphetamine (TT-SMA) with aluminum hydroxide (alum) and entolimod, a Toll-Like Receptor-5 agonist.
Purpose of the Study:
- To optimize an anti-MA vaccine formulation by evaluating different doses of entolimod for enhanced immunogenicity.
- To assess the functional efficacy of the vaccine in reducing MA-induced locomotor activity.
- To investigate the vaccine's ability to attenuate MA-induced cardiovascular effects and drug-seeking behavior through passive immunization.
Main Methods:
- Mice were vaccinated with TT-SMA+alum and varying entolimod doses to find an optimal immunogenic concentration.
- MA-induced locomotor activation was measured in mice to evaluate functional effects.
- Passive immunization studies in rats assessed the vaccine-generated antibodies' impact on MA-induced cardiovascular responses and relapse behaviors.
Main Results:
- Peak antibody levels were observed at 10 weeks post-vaccination with the combined formulation.
- Vaccinated mice showed significantly reduced MA-induced locomotor activation, correlating with antibody levels.
- Passive immunization attenuated MA-induced increases in mean arterial pressure and reduced drug-seeking behavior in rats.
Conclusions:
- The developed anti-MA vaccine formulation demonstrates significant efficacy in preclinical models.
- Results support the potential of this vaccine as a novel therapeutic strategy for preventing relapse in individuals with MUD.
- Further development is warranted to translate these findings into a human clinical treatment for MUD.
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