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Vaccines for fentanyl analogs are in development

Experimental vaccines may provide protection against some fentanyl analogs, according to a new study in rats. 

Vaccines against opioids are in development, and some have reached early clinical testing. Vaccines rely on exposure to a “hapten,” or molecular fragment, which mimics a critical binding region of the opioid, bound to an immunogenic carrier protein; the immune system then produces polyclonal antibodies to the hapten that, upon exposure to the real drug, can bind and neutralize it, reducing the amount of drug reaching central-nervous-system targets. 

But the myriad of existing and possible analogs of fentanyl provide a challenge to vaccine development. “Because vaccine-induced antibodies are highly specific for their target opioid, it is critical for vaccine research to stay ahead of structurally diverse fentanyl analogues,” according to the study authors. To begin to address that challenge, the authors prepared multiple hapten-carrier conjugates, based on the structures of fentanyl, alfentanil, sufentanil, and acetylfentanyl, and tested their efficacy in rats. 

The vaccines were effective against each of the analogs except alfentanil, reducing antinociceptive effects, respiratory depression, and bradycardia caused by the opioids. 

“Overall,” the authors concluded, “these results highlight the importance of evaluating the applicability of antifentanyl vaccines in vivo both for broad efficacy against a variety of fentanyl analogues of clinical interest and for efficacy of fentanyl vaccines against high doses of fentanyl relevant for use as a strategy for overdose prevention.”

Baehr C, Robinson C, Kassick A, et al. Preclinical efficacy and selectivity of vaccines targeting fentanyl, alfentanil, sufentanil, and acetylfentanyl in rats. ACS Omega. 2022;7(19):16584-16592.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118421/