Heroin vaccine works in primates

P. Rajendran

Paul Bremer and Kim Janda of TSRI

Paul Bremer and Kim Janda of The Scripps Research Institute. (Photo: Faith Hark)

Around the time opioid prescriptions were peaking in 2011, presaging a new wave of addicts, Kim Janda and his group at the Scripps Research Institute came up with a heroin vaccine that kills the drug’s high. It has now moved up the chain of pre-clinical testing so that vaccinated non-human primates do not get a high from heroin.

The societal cost of heroin use was recently estimated at about $51,000 per person, or $51 billion in 2015 dollars.

This, the first opioid vaccine to get this far in pre-clinical research, speaks well for the more than 30 years Janda has put into generating vaccines against drugs. Janda is the Ely R. Callaway Jr. Professor of Chemistry and a member of the Skaggs Institute for Chemical Biology at TSRI.

The results are even more encouraging because a study on the penchant of rhesus monkeys to self-administer cocaine, conducted along with teams at Cornell and Columbia universities, did not go as well.

Still, using different antibodies, Janda’s team has shown a similar immune responses against fentanyl, methamphetamine and nicotine, too – all in rodents, though.

Heroin tagged with proteins that attract the immune system ensure there's not enough to get a high from

If heroin is tagged with larger proteins that make it a juicier target for the immune system there is not enough of the drug to find its way to the brain and still cause a high

The current trials, conducted on rhesus monkeys at the Virginia Commonwealth University, suggests the heroin vaccine works on primates, too. While the antibodies best held off heroin’s insidious high in the monkeys in the first month, the protective effect lingered on for seven more.

This is known because two of the four primates had been given the same vaccine seven months earlier. These two were far more responsive to the vaccine the second time around, suggesting long-term immunity could result.

Four subjects may be deemed too few but then monkey research is expensive.

The study’s first author Paul Bremer said the reviewers understood some of the concerns but could see that some earlier research on monkeys and the unambiguous results this time suggested the vaccine did mute the drug’s high.

“You can say it’s a limitation, but based on how well it works in four [monkeys], I don’t see it being a big problem,” he says.

Injected heroin tends to quickly break down into 6-acetylmorphine and then morphine. Earlier attempts at vaccines targeted a key area of the morphine molecule. The Janda team’s antibodies bind to heroin and 6-acetylmorphine strongly, and to morphine to a lesser extent. But this also means the vaccine is not very effective against other opioids that have different breakdown products, ones these antibodies will not target.

“We believe this vaccine candidate will prove safe for human trials,” Janda said in a TSRI press release, pointing out that the components of the vaccine have either already been approved by the FDA or have passed safety tests in previous trials.

“These steps let us put our best foot forward when we went into the primate study,” he said.

Bremer said the new heroin vaccine is an improved one since some tweaking ensured the antibody bound better to the drug.

For a variety of reasons, over the years, funding has been slow to come by, even though Janda has worked with another heavyweight in drug research at Scripps, George Koob, now the director of the National Institute on Alcohol Abuse and Alcoholism.

“NIDA (The National Institute on Drug Abuse) have been pretty good giving us funds for pre-clinical trials,” says Bremer. There were some problem, though, getting a pharmaceutical company to work with them on the trials but he is not particularly bothered.

“As a researcher, I – and Kim Janda – have done everything at the pre-clinical [level],” he says. The subtext: they have pushed the frontier farther; it is for others to make use of what they have found.

The research was published in the Journal of the American Chemical Society.

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