THE idea of vaccinating drug addicts against their affliction is an intriguing one. In principle, it should not be too hard. The immune system works, in part, by making antibodies that are specific to particular sorts of hostile molecule. Such antibodies recognise and attach themselves to these molecules, rendering them harmless. Vaccines work by presenting the immune system with novel targets, so that it can learn to react to them if it comes across them again.
The problem is that the molecules antibodies recognise and react to are the big ones, such as proteins, that are characteristic of bacteria, viruses and other infectious agents. Small molecules, such as drugs, go unnoticed. But not for much longer, if Kim Janda of the Scripps Research Institute in San Diego has his way. In a paper just published in the Journal of the American Chemical Society, Dr Janda and his colleagues suggest how a vaccine against methamphetamine, a popular street drug, might be made. If their method works, it would open the possibility of vaccinating people against other drugs, too.
The idea of a methamphetamine vaccine is not new. The problem is getting the immune system to pay attention to a molecule that is such a small target. The way that has been tried in the past is to build the vaccine from several components.
First, there is a large carrier protein that forms a platform for the target. Then there is the target itself, a set of smaller molecules called haptens that are attached to the carrier. These may either be the drug in question or some analogue of it that, for one reason or another, is reckoned to have a better chance of training the immune system. Finally, there is a chemical cocktail called an adjuvant that helps get the immune system to pay attention to the carrier protein and the haptens.
Dr Janda noticed that past experiments on methamphetamine vaccines had all revolved around tweaking either the carrier protein or the adjuvant, rather than tinkering with the haptens. He thought he might be able to change that, on the basis of work he had carried out previously, trying to design a vaccine against nicotine. In particular, nicotine is a highly flexible molecule. That makes it hard for the immune system to recognise. To overcome this, his team on the nicotine project had to work out how to fix their haptens to the carrier protein in a way that rendered them less capable of twisting and turning, and thus made them easier for the immune system to identify.
In the new study, Dr Janda and his colleagues report that they have performed a similar trick with methamphetamine haptens. They used computer models to visualise the haptens in three dimensions and thus work out how the molecules could be rearranged such that they could not spring, twist or turn when being examined by the immune system. In light of this information they designed six new methamphetamine-like haptens. Once built, they attached the new hapten molecules to carrier proteins, mixed them with adjuvant, injected the results into mice and waited. After several weeks they tested the mice to see if the animals' blood contained antibodies to methamphetamine.
Of the six new haptens, three successfully provoked the mice to make such antibodies. As a bonus, one of those three also stimulated the production of antibodies against another widely used drug, amphetamine. That is still a long way from providing a working vaccine, but it is an important step forward. And if human immune systems react in the same way to the new vaccines as murine ones do, the day when a drug addict might be offered vaccination rather than opprobrium will have come a little closer.