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Consequence of Hapten Stereochemistry: An Efficacious Methamphetamine Vaccine
Margaret E Olson1, Takashi Sugane1, Bin Zhou1
1Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, and Worm Institute of Research and Medicine (WIRM) , The Scripps Research Institute , 10550 N. Torrey Pines Road , La Jolla , California 92037 , United States of America.
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 (S)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 (S)-stereochemistry in METH hapten design for optimal protection.
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