Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine
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)...
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MDPI AG
2022-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/9/1508 |
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| author | Colin N. Haile Kurt J. Varner Xia Huijing Reetakshi Arora Frank M. Orson Thomas R. Kosten Therese A. Kosten |
| author_facet | Colin N. Haile Kurt J. Varner Xia Huijing Reetakshi Arora Frank M. Orson Thomas R. Kosten Therese A. Kosten |
| author_sort | Colin N. Haile |
| collection | DOAJ |
| description | 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">μ</mi></semantics></math></inline-formula>g). 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. |
| first_indexed | 2024-03-09T22:16:33Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T22:16:33Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
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| series | Vaccines |
| spelling | doaj.art-b78660c9227a43e9b51847c33f5f5a462023-11-23T19:22:20ZengMDPI AGVaccines2076-393X2022-09-01109150810.3390/vaccines10091508Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of MethamphetamineColin N. Haile0Kurt J. Varner1Xia Huijing2Reetakshi Arora3Frank M. Orson4Thomas R. Kosten5Therese A. Kosten6Department of Psychology/TIMES, University of Houston, Houston, TX 77204, USADepartment of Pharmacology and Experimental Therapeutics and the Cardiovascular Center of Excellence, LSUHSC, New Orleans, LA 70112, USADepartment of Pharmacology and Experimental Therapeutics and the Cardiovascular Center of Excellence, LSUHSC, New Orleans, LA 70112, USAThe Michael E DeBakey Veteran’s Affairs Medical Center, Houston, TX 77030, USAThe Michael E DeBakey Veteran’s Affairs Medical Center, Houston, TX 77030, USAThe Michael E DeBakey Veteran’s Affairs Medical Center, Houston, TX 77030, USADepartment of Psychology/TIMES, University of Houston, Houston, TX 77204, USABackground: 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">μ</mi></semantics></math></inline-formula>g). 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.https://www.mdpi.com/2076-393X/10/9/1508conjugate vaccineentolimodmethamphetamine use disorderlocomotor activitydrug reinstatementmedication development |
| spellingShingle | Colin N. Haile Kurt J. Varner Xia Huijing Reetakshi Arora Frank M. Orson Thomas R. Kosten Therese A. Kosten Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine Vaccines conjugate vaccine entolimod methamphetamine use disorder locomotor activity drug reinstatement medication development |
| title | Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine |
| title_full | Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine |
| title_fullStr | Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine |
| title_full_unstemmed | Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine |
| title_short | Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine |
| title_sort | active and passive immunization with an anti methamphetamine vaccine attenuates the behavioral and cardiovascular effects of methamphetamine |
| topic | conjugate vaccine entolimod methamphetamine use disorder locomotor activity drug reinstatement medication development |
| url | https://www.mdpi.com/2076-393X/10/9/1508 |
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