posted on 2023-12-22, 13:36authored byDaihyun Song, Bethany Crouse, Jennifer Vigliaturo, Mariah M. Wu, Dagny Heimisdottir, Andrew J. Kassick, Saadyah E. Averick, Michael D. Raleigh, Marco Pravetoni
Illicit drug mixtures containing
opioids and stimulants have been
responsible for the majority of fatal drug overdoses among occasional
users, and those with either opioid use disorder (OUD) or substance
use disorder (SUD). As a complementary strategy to current pharmacotherapies,
active immunization with conjugate vaccines has been proposed as a
viable intervention to treat OUD as well as other SUD for which there
are either limited or no treatment options. Vaccination against opioids
and stimulants could help address the limitations of current medications
(e.g., patient access, compliance, misuse liability, and safety) by
providing an additional tool to prevent drug misuse and/or overdoses.
However, more research is needed to fully understand the potential
benefits and limitations of using vaccines to treat SUD and overdose
and to inform us on how to deploy this strategy in the field. Previous
reports have shown promise by combining two vaccines into bivalent
vaccine formulations to concurrently target multiple drugs. Here,
multiple individual candidate monovalent vaccines were incrementally
combined in multivalent vaccine formulations to simultaneously target
fentanyl, carfentanil, oxycodone, heroin, methamphetamine, and their
analogs or metabolites. Bi-, tri-, and quadrivalent vaccine formulations
induced the formation of independent serum antibody responses against
their respective opioid targets and selectively attenuated the distribution
of each individual drug to the brain in mice and rats. Results indicate
that a single injection of an admixed multivalent vaccine formulation
may be more effective than coinjecting multiple monovalent vaccines
at multiple sites. Finally, adding a methamphetamine conjugate vaccine
to an quadrivalent opioid vaccine in a pentavalent formulation did
not interfere with the production of effective antiopioid IgG antibodies.
Multivalent vaccines could provide multifaceted, yet selective, protection
against polydrug use and exposure.