A Highly Efficacious Carfentanil Vaccine That Blunts Opioid-Induced Antinociception and Respiratory Depression

Abstract

The opioid epidemic remains a dire public health crisis with millions of people currently suffering from opioid use disorder (OUD) and tens of thousands dying each year. Synthetic opioids are most responsible for the crisis because of their extreme potency and ease of manufacture. Carfentanil for example has an estimated potency 10,000 times greater than morphine and thus is highly dangerous for human use. Herein, we report two synthetic opioid vaccines that elicited high-affinity antibodies against carfentanil and fentanyl with cross-reactivity to other synthetic opioids in mice and offered protection against opioid-induced respiratory depression, the primary cause of overdose deaths. These vaccines also successfully diminished drug biodistribution to the brain and shielded against opioid analgesic effects. Collectively, these findings provide new insights into the development of immunotherapeutic strategies aimed at opioid abuse and overdose.

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

“… 14 , 16 Evaluations of multitarget vaccines such as heroin/fentanyl vaccines have shown specificity of serum antibodies for multiple opioid targets but did not assess efficacy against fentanyl analogues other than those targeted by the vaccine. 27 , 28 , 30 − 32 Recent vaccines targeting carfentanil have demonstrated in vitro cross-reactivity against multiple fentanyl analogues and in vivo efficacy against both fentanyl and carfentanil, 29 and against fentanyl–carfentanil admixtures, 100 but were not evaluated in vivo against other fentanyl analogues.…”

A Vaccine against Benzimidazole-Derived New Psychoactive Substances That Are More Potent Than Fentanyl

“…The conjugate vaccines implemented CpG ODN 1826 and alum because this adjuvant cocktail has been reported to be highly effective in immunopharmacotherapeutic vaccines . Antigen and adjuvant concentrations followed previous immunopharmacotherapy studies ,, and are well within standard concentrations . All vaccines were made fresh on the day of administration and were injected IP into 7-week-old female BALB/cByJ mice on weeks 0, 2, and 4 (Figure S2).…”

Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse

“…Pretreatment with the opioid receptor antagonist naltrexone decreases the seeking of fentanyl and heroin but not carfentanil [ 126 ]. Recently, two synthetic vaccines, Carfen- ester -TT and Carfen- p-phenyl -TT, have been shown to reduce carfentanil biodistribution in the brain and blunt carfentanil-induced antinociception and respiratory depression [ 127 ].…”