Scientists see great promise in the idea of combining vaccines with other interventions to improve patient outcomes in addiction therapy.
A successful anti-drug vaccine will induce an immune response that blocks the target drug from entering the brain.
A patient who has been vaccinated will obtain no reward or relief of craving from taking the target drug, and so will have reduced motivation to continue further in relapse.
The major challenge in making an anti-drug vaccine is that the cells that make antibodies, B lymphocytes, normally do not detect or respond to drugs.
To mobilize the B lymphocytes to generate an antibody response to the target drug, vaccine developers combine two components:
- A modified molecule of the target drug, called a hapten, to provide a template for the formation of anti-drug antibodies
- and a carrier protein to stimulate the antibody-forming B lymphocytes.
Typically, an anti-drug vaccine is administered together with an adjuvant, which may be another protein or another substance.
The adjuvant enhances the strength of the antibody response.
There are billions of B-lymphocytes, and each one expresses a different antibody on its surface.
Among all these, there is one whose antibody corresponds to the hapten as a lock corresponds to a key.
Stimulated by the carrier protein in the vaccine, this B-lymphocyte binds to the hapten.
This high-affinity binding triggers a change in the B-lymphocyte.
The B-lymphocyte draws the vaccine-antibody complex into itself, then transforms into a plasmocyte, which manufactures and releases anti-drug antibody.
The plasmocyte rapidly multiplies by cloning, resulting in the release of massive quantities of anti-drug antibody into the bloodstream.
Anti-drug vaccines take advantage of a tissue filter that surrounds the blood vessels in the brain.
The filter, called the blood-brain barrier, protects the brain from exposure to many potentially harmful substances circulating in the blood.
The barrier normally does not block out drug molecules, which easily pass through it despite being harmful.
If an individual has been vaccinated however, the antibodies produced by the vaccine, bind to the drug molecules in the bloodstream.
The compound drug-antibody molecules are too big to go through the blood brain barrier.
Hence the drug cannot enter the brain and cannot produce psychoactive or addictive effects.
An anti-drug vaccine will be clinically useful if the antibody response it induces is sufficiently strong and long-lasting.
To prevent the drug from having psychoactive effects, the antibody blood concentration, or titer, must be high enough to intercept all or almost all of the target drug molecules before they reach the blood-brain barrier.
To allow booster shots to be given at reasonable intervals, the titer must remain at such a level for weeks, months, or more.
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