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Fatal is claiming the lives of tens of thousands of Americans every year in what experts have described as the “worst crisis America has ever faced.”
But it could become a thing of the past thanks to a new vaccine that would be given to high-risk drug users months or possibly years before they overdose.
The vaccine, which will likely be given through several injections, essentially teaches the immune system how to prevent opioids from cutting off oxygen to the brain.
The researchers say they expect human trials to begin in “early 2024.” The fentanyl vaccine would differ from the antidote Narcan, which is administered in case of an overdose and has already been approved by the Food and Drug Association (FDA).
Molecular biologist Jay Evans of the University of Montana (above) expects his group’s vaccines targeting heroin and fentanyl to enter human trials “in early 2024.”
Both heroin and fentanyl bind to opioid receptors in areas of the brain that control pain and emotions. During an overdose, the brain is deprived of oxygen, which kills the neurons. An opioid vaccine would neutralize the chemical with antibodies while it is still in the bloodstream.
In animal studies, including one published this July in the journal Nature npj Vaccinesthe researchers were able to show that these fentanyl vaccines could be improved with the addition of a second small molecule called an adjuvant.
But those tests will have to be safe and repeatable in humans before anyone can line up for their own vaccines.
The team, led by researchers at the University of Montana, has created two new vaccines, the second targeting heroin overdoses.
Both heroin and fentanyl bind to and deaden areas of the brain that control pain and emotions. But during an overdose, these chemicals starve the brain of oxygen, killing neurons.
The new vaccines, similar to competing fentanyl vaccines research elsewhere, are designed to neutralize opioid chemicals with antibodies while these compounds are still in the bloodstream.
“Once we establish safety and early efficacy in these early clinical trials,” said University of Montana (UM) molecular biologist Jay Evans, “we hope to develop a combined multivalent vaccine targeting both heroin and fentanyl.”
The United States is currently in the midst of a fentanyl epidemic, with around 150 Americans dying each day from the synthetic opioid. according to the US Centers for Disease Control and Prevention (CDC)..
The CDC estimates that among the 107,081 reported drug overdose deaths in the United States in 2022, more than two-thirds or more than 72,000 could be attributed to synthetic opioids such as fentanyl.
Evans, who is also a co-founder of the new company Inimmune designed to bring these drugs to market, has focused his UM team on creating more adjuvants, substances they hope will further increase the efficacy of the vaccines.
“Our adjuvants enhance the response to the vaccine, providing stronger, longer lasting immunity,” said Evans, whose official title is Director of the UM Center for Translational Medicine.
Evans’ UM team patented the INI-4001 adjuvant, which will be just one facet of the final vaccine cocktails.
Fentanyl has invaded some American communities and was responsible for 71,000 drug overdose deaths in 2021. Pictured: A homeless man in Seattle, Washington, smokes fentanyl.
“We have worked closely with researchers at Inimmune, the University of Minnesota, the University of Washington, the Hennepin Institute for Health Research, and Columbia University over the past few years to design and optimize anti-opioid vaccines to move toward human clinical trials,” he claimed. .
The vaccine itself works by stimulating the T cells of the immune system to create antibodies that bind to fentanyl in the bloodstream.
These immune proteins trap the drug as it enters the body and prevent it from spreading further and causing harm. It is then processed in the kidney and eliminated from the body.
“Antibodies produced by active immunization with an opioid vaccine sequester the opioid in the blood and prevent it from crossing the blood-brain barrier,” according to Evans’ research partner. Dr Marco Pravetoni at the University of Washington, where he directs the Center for Drug Development for Substance Use Disorders.
“The first vaccine will target heroin,” Evans said, “followed shortly thereafter by a fentanyl vaccine in phase I clinical trials.”
These Phase 1 human trials, he noted, will be conducted by the group’s collaborator, Dr. Sandra Comer, of Columbia University in New York.
Finding the right subjects, patients currently using fentanyl or heroin, could take six months or more.
And the process will have to move slowly to protect the health and safety of these human subjects.
Evans said that phase 1 trials will involve very gradual increases in the dose of the vaccine.
“We start with the lowest dose, a dose that may not be effective,” Evans said.
‘Phase I clinical trials focus on safety. When the first dose cohort is complete, a data safety monitoring board reviews the data and approves testing at the next dose level if the vaccine is safe. The process takes time until dose levels that are safe and effective are reached.’
Evan added that Dr. Comer and others will also be following trial patients to assess “how long opioid antibodies will last.”
If those tests prove successful and safe, Phase 2 human trials will be challenged to determine details such as the number of doses needed for effective protection against overdose, as well as the proper time required between doses.
Then would come Phase 3: a large cohort study with many participants, designed to help the FDA decide whether the life-saving benefits of the vaccine outweigh the potential risks of side effects.
But a similar vaccine, targeting the prescription opioid oxycodone, is already blazing a trail ahead of vaccines against heroin and fentanyl.
Dr. Pravetoni, Evans’s research partner at the University of Washington, introduced the oxycodone vaccine into Phase I trials with Dr. Comer at Columbia in 2021.
“Our vaccines are designed to neutralize the target opioid while avoiding critical drugs such as methadone, buprenorphine, naltrexone and naloxone,” said Evans, “which are used in opioid addiction treatment and opioid reversal.” overdose”.
That needle is threaded by vaccines called ‘haptens’ and ‘drug conjugates’ developed by Dr. Pravetoni, which can stimulate the body’s immune system to produce antibodies only against target opioids.
Although these advances have shown great success in animal tests and other laboratory-scale experiments, Evans cautioned that many regulatory steps must be taken before these vaccines can begin to help users who are currently at risk.
“It takes a long time (years) to get to a final approved product,” he said.
‘Based on the efficacy data we see in our preclinical data and the established safety profile in animal models, we are very hopeful that these vaccines will be successful. But there is still a lot of work to be done.”