Consequence of Hapten Stereochemistry: An Efficacious Methamphetamine Vaccine

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Sep 4

PMID 31479256

Citations 6

Authors

Margaret E Olson

Takashi Sugane

Bin Zhou

Kim D Janda

Affiliations

Soon will be listed here.

Abstract

Recent trends in methamphetamine (METH) misuse and overdose suggest society is inadvertently overlooking a brewing METH crisis. In the past decade, psychostimulant-related lethal overdoses and hospitalizations have skyrocketed 127 and 245%, respectively. Unlike the opioid crisis, no pharmaceutical interventions are available for treating METH use disorder or reversing overdose. Herein, we report the first active vaccine that offers protection from lethal (+)-METH challenge in male Swiss Webster mice. This vaccine formulation of ()MLMH-TT adjuvanted with CpG ODN 1826 + alum successfully raised anti-METH antibodies in high titers, reduced (+)-METH distribution to the brain, and lowered (+)-METH-associated stereotypies in a hyperlocomotion assay. A comparison of enantiomeric haptens and the racemate elucidated the importance of employing ()-stereochemistry in METH hapten design for optimal protection.

Citing Articles

Expedited Evaluation of Conformational Stability-Heterogeneity Associations for Crude Polyclonal Antibodies in Response to Conjugate Vaccines.

Zheng Z, Ma M, Jia Y, Cui Y, Zhao R, Li S Anal Chem. 2023; 95(29):10895-10902.

PMID: 37433088 PMC: 10695093. DOI: 10.1021/acs.analchem.3c00223.

Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine.

Haile C, Varner K, Huijing X, Arora R, Orson F, Kosten T Vaccines (Basel). 2022; 10(9).

PMID: 36146588 PMC: 9503672. DOI: 10.3390/vaccines10091508.

Broadly Neutralizing Synthetic Cannabinoid Vaccines.

Lin M, Lee J, Blake S, Ellis B, Eubanks L, Janda K JACS Au. 2021; 1(1):31-40.

PMID: 34467269 PMC: 8395583. DOI: 10.1021/jacsau.0c00057.

Immunopharmacotherapeutic advancements in addressing methamphetamine abuse.

Lee J, Janda K RSC Chem Biol. 2021; 2(1):77-93.

PMID: 34458776 PMC: 8341824. DOI: 10.1039/d0cb00165a.

Sulfonate-isosteric replacement examined within heroin-hapten vaccine design.

Belz T, Bremer P, Zhou B, Blake S, Ellis B, Eubanks L Bioorg Med Chem Lett. 2020; 30(17):127388.

PMID: 32738981 PMC: 7398700. DOI: 10.1016/j.bmcl.2020.127388.

References

Peterson E, Gunnell M, Che Y, Goforth R, Carroll F, Henry R . Using hapten design to discover therapeutic monoclonal antibodies for treating methamphetamine abuse. J Pharmacol Exp Ther. 2007; 322(1):30-9. DOI: 10.1124/jpet.106.117150. View

Moreno A, Mayorov A, Janda K . Impact of distinct chemical structures for the development of a methamphetamine vaccine. J Am Chem Soc. 2011; 133(17):6587-95. PMC: 3090292. DOI: 10.1021/ja108807j. View

Gooyit M, Miranda P, Wenthur C, Ducime A, Janda K . Influencing Antibody-Mediated Attenuation of Methamphetamine CNS Distribution through Vaccine Linker Design. ACS Chem Neurosci. 2016; 8(3):468-472. PMC: 5711417. DOI: 10.1021/acschemneuro.6b00389. View

Nguyen J, Bremer P, Hwang C, Vandewater S, Collins K, Creehan K . Effective active vaccination against methamphetamine in female rats. Drug Alcohol Depend. 2017; 175:179-186. PMC: 5484075. DOI: 10.1016/j.drugalcdep.2017.03.005. View

Byrnes-Blake K, Carroll F, Abraham P, Owens S . Generation of anti-(+)methamphetamine antibodies is not impeded by (+)methamphetamine administration during active immunization of rats. Int Immunopharmacol. 2001; 1(2):329-38. DOI: 10.1016/s1567-5769(00)00019-9. View

Shen X, Kosten T, Lopez A, Kinsey B, Kosten T, Orson F . A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug Alcohol Depend. 2012; 129(1-2):41-8. PMC: 3563850. DOI: 10.1016/j.drugalcdep.2012.09.007. View

Miller M, Aarde S, Moreno A, Creehan K, Janda K, Taffe M . Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug Alcohol Depend. 2015; 153:29-36. PMC: 4509945. DOI: 10.1016/j.drugalcdep.2015.06.014. View

Sulzer D, Sonders M, Poulsen N, Galli A . Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005; 75(6):406-33. DOI: 10.1016/j.pneurobio.2005.04.003. View

Collins K, Schlosburg J, Bremer P, Janda K . Methamphetamine Vaccines: Improvement through Hapten Design. J Med Chem. 2016; 59(8):3878-85. PMC: 5895457. DOI: 10.1021/acs.jmedchem.6b00084. View

10.

Stevens M, Gunnell M, Tawney R, Owens S . Optimization of a methamphetamine conjugate vaccine for antibody production in mice. Int Immunopharmacol. 2016; 35:137-141. PMC: 4851881. DOI: 10.1016/j.intimp.2016.03.028. View

11.

Harris J, Baldessarini R . Uptake of (3H)-catecholamines by homogenates of rat corpus striatum and cerebral cortex: effects of amphetamine analogues. Neuropharmacology. 1973; 12(7):669-79. DOI: 10.1016/0028-3908(73)90120-2. View

12.

Carroll F, Blough B, Pidaparthi R, Abraham P, Gong P, Deng L . Synthesis of mercapto-(+)-methamphetamine haptens and their use for obtaining improved epitope density on (+)-methamphetamine conjugate vaccines. J Med Chem. 2011; 54(14):5221-8. PMC: 3141093. DOI: 10.1021/jm2004943. View

13.

Ruedi-Bettschen D, Wood S, Gunnell M, West C, Pidaparthi R, Carroll F . Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food. Vaccine. 2013; 31(41):4596-602. PMC: 3835592. DOI: 10.1016/j.vaccine.2013.07.038. View

14.

Miller M, Moreno A, Aarde S, Creehan K, Vandewater S, Vaillancourt B . A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biol Psychiatry. 2012; 73(8):721-8. PMC: 3561477. DOI: 10.1016/j.biopsych.2012.09.010. View