Will Trial Vaccine Slay Meth Dragon?
Breathless headlines greet each new experimental addiction "vaccine." But such efforts face tougher obstacles than many realize.
Last week's news that an experimental vaccine against methamphetamine shows efficacy in animal trials made big headlines. It seems a far better bet than any previous anti-meth shots: “This is an early-stage study, but its results are comparable to those for other drug vaccines that have then gone to clinical trials,” said Michael Taffe, an associate professor in The Scripps Research Institute, who co-authored the study. Vaccines have long captured the public imagination as "magic bullets," but whether the news is more hype than hope is a question the coverage largely fails to address. This is peculiar, since a vaccine's progress from success in rats to efficacy in humans requires a quantum leap, and over four decades no vaccine for any drug has made it. Still, Scripps has impressive credentials: the La Jolla, Calif., research center has one of the nation's most robust drug vaccine programs. It also has Dr. Kim Janda, who was a leading pioneer of the concept of addiction vaccines, long before addiction was even viewed as a medical condition.
Most trial addiction vaccines are based on the common adjutant-vaccine model. This approach introduces into the blood a sample (live or lab-made) of the drug molecule, to spark the immune system into mounting an antibody defense against drug use. A major challenge is that most drug molecules are tiny enough to sneak past the immune system. So the molecules have to be artificially bulked up, both in size (by means of a harmless protein “platform”) and in activity (by means of an “adjuvant”—a copycat of the drug molecule that amplifies its effect). This three-piece invader reliably triggers a drug-specific antibody response. "The antibody is like a sponge," Janda said. "The drug comes in and it's soaked up, and you try to soak up as much as you can before it crosses the blood-brain barrier." (Most experts agree that a vaccine for alcoholism is unfeasible, because ethanol molecules are simply too small to spark an antibody response or even to attach a platform or adjutant to.) Block a drug’s access to the brain and you block that drug’s effect. And an absent or reduced high will further incentivize an addict who is already highly motivated (crucially) to abstain. So why has every fledgling addiction vaccine failed?
Climbing the evolutionary ladder from rodent to human is very rare (one in 1,000) for any experimental compound. Weapons that work in rats are usually either too blunt or too toxic to work in the human body's immensely complex and interconnected systems. Addiction vaccines that do work in humans also tend to have a high nonresponse rate, partly because of the great variability in drug-specific antibody formation. For example, the most successful exploratory cocaine vaccine fails to trigger an adequate immune response in 25% of subjects. But the mysteries of the human body may be less problematic than those of the human brain and mind. For one, the drive to experience euphoric highs can be all-consuming. Predictably, many subjects in clinical trials relapse soon after getting the vaccine, and face the added complication that to obtain the desired familiar pleasure state—and override the vaccine's anti-drug blockade—they then need to take higher doses than before. The risks of chasing the old high include overdose, spending excessive amounts of money, and switching drugs—meth for coke, say. In addition, the anti-drug effect of most addiction vaccines is only temporary, meaning periodic shot repeats are required—perhaps monthly in the case of the Scripps meth vaccine—posing a reliability test that many addicts are unprepared for.
That the neurochemistry and the psychology of craving remain out of reach of vaccines' power is a serious stumbling block. So is the glaring fact that no vaccine can soothe the myriad sources of physical and emotional pain that lead to self-medication in the first place. Where is the pill for poverty or violence? Money is, as ever, another obstacle: the drug industry balks at investing in treatments for addicts partly because they are viewed as too risky—impulsive, noncompliant, even criminal. The exception is smokers: several big pharmas have advanced nicotine vaccines into Phase III clinical trials. (A cocaine vaccine that doesn't require redosing has also reached late-stage testing.)