Drug-related fatal overdoses have significantly increased in the past decade due to the widespread availability of illicit
fentanyl and other potent synthetic
opioids such as
carfentanil. Deliberate or accidental consumption or exposure to
carfentanil,
fentanyl, and their mixture induces
respiratory depression and
bradycardia that can be difficult to reverse with the
opioid receptor antagonist naloxone.
Vaccines offer a promising strategy to reduce the incidence of fatalities associated with
fentanyl-related substances, as well as treatment for
opioid use disorder (OUD). This study reports monovalent and bivalent vaccination strategies that elicit polyclonal antibody responses effective in protecting against the pharmacological actions of
carfentanil,
fentanyl, or
carfentanil/
fentanyl mixtures. Rats were prophylactically immunized with individual
conjugate vaccines containing either
carfentanil- or
fentanyl-based
haptens, or their combination in
bivalent vaccine formulations, and then challenged with
carfentanil,
fentanyl, or their mixture. First, these studies identified a lead
vaccine protective against
carfentanil-induced antinociception,
respiratory depression, and
bradycardia. Then, efficacy against both
carfentanil and
fentanyl was achieved through bivalent vaccination strategies that combined lead anti-
carfentanil and anti-
fentanyl vaccines via either heterologous prime/boost or co-administration immunization regimens. These preclinical data support the development of
vaccines as a viable strategy to prevent toxicity from exposure to excessive doses of
carfentanil,
fentanyl, or their mixtures.