Vaccine to protect from heroin high created
29 July 2011
Researchers at The Scripps Research Institute in the US have
developed a highly successful vaccine against a heroin high and have
proven its therapeutic potential in animal models.
The new study demonstrates how a novel vaccine produces
antibodies (a kind of immune molecule) that stop not only heroin but
also other psychoactive compounds metabolized from heroin from
reaching the brain to produce euphoric effects.
“In my 25 years of making drug-of-abuse vaccines, I haven’t seen
such a strong immune response as I have with what we term a dynamic
anti-heroin vaccine,” said the study’s principal investigator, Kim
D. Janda, the Ely R. Callaway, Jr. Chair in Chemistry and a member
of The Skaggs Institute for Chemical Biology at Scripps Research.
"It is just extremely effective. The hope is that such a protective
vaccine will be an effective therapeutic option for those trying to
break their addiction to heroin."
“We saw a very robust and specific response from this heroin
vaccine,” said George F. Koob, chair of the Scripps Research
Committee on the Neurobiology of Addictive Disorders and a co-author
of the new study. “I think a humanized version could be of real help
to those who need and want it.”
A worldwide epidemic
While injection drug abuse is a debilitating worldwide epidemic,
heroin abuse and addiction are especially destructive, with costs
estimated at US$22 billion in the United States due to loss of
productivity, criminal activity, medical care, and social welfare,
the authors say in their study.
Heroin abuse and addiction are also driving forces in the spread
of HIV through needle sharing.
Using an approach termed "immunopharmacotherapy," Janda and his
Scripps Research colleagues previously created vaccines that used
immune molecules to blunt the effects of other abused drugs such as
cocaine, methamphetamine, and nicotine. Human clinical trials are
under way for the cocaine and nicotine vaccines.
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
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
“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-administer” heroin by pressing on a lever after several
booster shots of the vaccine. Only three of the seven rats that
received the heroin vaccine self-administered heroin. In contrast,
all of the control rats, including those given the morphine vaccine,
self-administered the drug.
The effect of the heroin vaccine “was very dramatic; as dramatic
as we have ever seen in experiments of this kind,” said Koob. “To
have an animal vaccinated and not show a response to heroin is
The team also found that the heroin vaccine was highly specific,
meaning that it only produced an antibody response to heroin and
6AM, and not to the other opioid-related drugs tested, such as
oxycodone as well as drugs used for opioid dependence—methadone,
naltrexone, and naloxone. “The importance of this,” said Janda, “is
that it indicates these vaccines could be used in combination with
other heroin rehabilitation therapies.”
The Scripps Research team has recently begun an exciting
collaboration with researchers at the Walter Reed Army Institute of
Research to see if it is feasible to develop a dual-purpose vaccine
against HIV and for the treatment of heroin addiction in a single
shot, Janda said.
G. Neil Stowe, Leandro F. Vendruscolo, Scott Edwards, Joel E.
Schlosburg, Kaushik K. Misra, Gery Schulteis, Alexander V. Mayorov,
Joseph S. Zakhari, George F. Koob, and Kim D. Janda. A Vaccine
Strategy that Induces Protective Immunity against Heroin. J.
Med. Chem., DOI: 10.1021/jm200461m.