Vaccine for the “zombie drug” developed as treatment for overdose

Chemical biologists have developed vaccines to block the effects of xylazine, a sedative for use in animals that is now being illicitly added to opioids, like fentanyl and heroin, in the US.

The vaccine has worked in mice, but no human trials have been undertaken.

Xylazine has severe adverse effects in humans, causing respiratory and central nervous system depression, and has led to a sharp rise in overdose deaths.

“We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says Kim Janda, professor of Chemistry at the Scripps Research Institute in the US, and senior author of a new study in the journal Chemical Communications.

“There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”

Researchers suspect xylazine works by reducing blood flow to the brain, among other areas of the body. It’s been nicknamed “zombie drug” because it also causes non-healing skin lesions and wounds, often located on the forearms and lower legs, which can require amputation in some cases.

The team developed a vaccine that in mice induces the immune system to create antibodies that bind to and reverse xylazine’s toxicity.

Normally, the xylazine molecule is too small to initiate an immune response on its own. To circumvent this problem, the scientists paired the drug molecule (called a hapten) with a carrier protein and an adjuvant – an ingredient used to boost an immune response to a vaccine.

The team tested 3 vaccine formulations containing a xylazine hapten combined with different protein types. They found that one vaccine (termed TT) significantly increased movement in mice given xylazine after 10 minutes, while TT and another vaccine (termed KLH) led to an improvement in breathing.

Because antibodies typically cannot cross the blood brain barrier, the vaccines limited xylazine’s detrimental effects by restricting its ability to reach receptors in the brain.

A provisional patent has been filed on the research. In the future, the team aims to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously.

“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda.

“This strategy could make a significant impact on the opioid epidemic.”  

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