Meth Vaccine Hunt Revamped

The search for vaccines that squelch the addictive drug methamphetamine is all about structure, a new report suggests (J. Am. Chem. Soc., DOI: 10.1021/ja108807j). No approved meth drug-abuse therapies exist, and efforts to develop vaccines that would keep the drug from reaching the brain where it is active have been largely ineffective. Kim D. Janda and colleagues at Scripps Research Institute have now used molecular modeling to guide their vaccine hunt. To generate antibodies that will bind and neutralize a small molecule such as meth, the small molecule must first be attached to a macromolecule such as albumin and then injected. In the case of meth, researchers have tried only one macromolecule attachment point so far—on the aromatic ring. Janda’s team designed and prepared molecules that have ring or side-chain attachment points and that mimic meth’s lowest energy conformations, which are more favorable for antibody binding. When injected into mice, three of the mimics, including MH2(R) (shown), elicited antibodies with high affinity for (+)-methamphetamine. The results suggest that, despite failures in the area, immunization with meth analogs might still be a useful approach for vaccine development, so long as the right molecules can be designed, Janda and coworkers write.