Open AccessBivalent Conjugate Vaccine Induces Dual Immunogenic Response That Attenuates Heroin and Fentanyl Effects in Mice
Author(s) -
Rodell C. Barrientos,
Connor Whalen,
Òscar Torres,
Agnieszka Sulima,
Eric W. Bow,
Essie Komla,
Zoltán Beck,
Arthur E. Jacobson,
Kenner C. Rice,
Gary R. Matyas
Publication year - 2021
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.1c00179
Subject(s) - fentanyl , chemistry , pharmacology , heroin , toxoid , hapten , bivalent (engine) , morphine , immunogenicity , tetanus , immunology , vaccination , medicine , antigen , drug , organic chemistry , metal
Opioid use disorders and fatal overdose due to consumption of fentanyl-laced heroin remain a major public health menace in the United States. Vaccination may serve as a promising potential remedy to combat accidental overdose and to mitigate the abuse potential of opioids. We previously reported the heroin and fentanyl monovalent vaccines carrying, respectively, a heroin hapten, 6-AmHap, and a fentanyl hapten, para- AmFenHap, conjugated to tetanus toxoid (TT). Herein, we describe the mixing of these antigens to formulate a bivalent vaccine adjuvanted with liposomes containing monophosphoryl lipid A (MPLA) adsorbed on aluminum hydroxide. Immunization of mice with the bivalent vaccine resulted in IgG titers of >10 5 against both haptens. The polyclonal sera bound heroin, 6-acetylmorphine, morphine, and fentanyl with dissociation constants ( K d ) of 0.25 to 0.50 nM. Mice were protected from the anti-nociceptive effects of heroin, fentanyl, and heroin +9% (w/w) fentanyl. No cross-reactivity to methadone and buprenorphine was observed in vivo . Naloxone remained efficacious in immunized mice. These results highlighted the potential of combining TT-6-AmHap and TT- para- AmFenHap to yield an efficacious bivalent vaccine that could ablate heroin and fentanyl effects. This vaccine warrants further testing to establish its potential translatability to humans.