Attempts by other researchers over the past four decades to create a clinically viable heroin vaccine, however, have fallen short, in part due to the fact that heroin is an elusive target metabolized into multiple substances each producing psychoactive effects.
An Innovative Approach
To overcome this problem, in the new study the Scripps Research team used a "dynamic" approach, targeting not only heroin itself, but also the chemical it quickly degrades into, 6-acetylmorphine (6AM), and morphine.
"Heroin is lipophilic and is rapidly degraded to 6AM," said G. Neil Stowe, a research associate in Janda's laboratory who is first author of the new study. "Both readily cross the blood-brain barrier and gain access to the opioid receptors in the brain."
The researchers linked a heroin-like hapten (a small molecule that elicits an immune response) to a generic carrier protein called keyhole limpet hemocyanin or KLH, and mixed it with Alum, an adjuvant (vaccine additive), to create a vaccine "cocktail." This mixture slowly degraded in the body, exposing the immune system to different psychoactive metabolites of heroin such as 6AM and morphine.
"Critically, the vaccine produces antibodies to a constantly changing drug target," said Stowe. "Such an approach has never before been engaged with drug-of-abuse vaccines."
To compare the results of a non-dynamic approach, the team also prepared a vaccine simply targeting morphine, a substance related to heroin. Both vaccines were then injected into rats and the effects were examined in Koob's laboratory.
The results showed that the rats rapidly generated robust polyclonal antibodies in response to the dynamic heroin vaccine.
In addition, the study found that addicted rats were less likely to "self-admini
|Contact: Mika Ono|
Scripps Research Institute