A Highly Efficacious Carfentanil Vaccine That Blunts Opioid-Induced Antinociception and Respiratory Depression. 2021

Lisa M Eubanks, and Steven Blake, and Yoshihiro Natori, and Beverly Ellis, and Paul T Bremer, and Kim D Janda
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, La Jolla, California 92037, United States.

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.

UI MeSH Term Description Entries
D009293 Opioid-Related Disorders Disorders related to or resulting from abuse or misuse of OPIOIDS. Opiate Addiction,Opiate Dependence,Opioid Misuse,Opioid Use Disorder,Prescription Opioid Abuse,Prescription Opioid Misuse,Addiction, Opioid,Dependence, Opioid,Opiate Abuse,Opioid Abuse,Opioid Addiction,Opioid Dependence,Abuse, Opiate,Abuse, Opioid,Abuse, Prescription Opioid,Addiction, Opiate,Dependence, Opiate,Disorder, Opioid Use,Misuse, Opioid,Misuse, Prescription Opioid,Opiate Abuses,Opioid Abuse, Prescription,Opioid Abuses,Opioid Addictions,Opioid Dependences,Opioid Misuses,Opioid Related Disorders,Opioid Use Disorders,Opioid-Related Disorder,Prescription Opioid Abuses,Prescription Opioid Misuses
D012131 Respiratory Insufficiency Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed) Acute Hypercapnic Respiratory Failure,Acute Hypoxemic Respiratory Failure,Hypercapnic Acute Respiratory Failure,Hypercapnic Respiratory Failure,Hypoxemic Acute Respiratory Failure,Hypoxemic Respiratory Failure,Respiratory Depression,Respiratory Failure,Ventilatory Depression,Depressions, Ventilatory,Failure, Hypercapnic Respiratory,Failure, Hypoxemic Respiratory,Failure, Respiratory,Hypercapnic Respiratory Failures,Hypoxemic Respiratory Failures,Respiratory Failure, Hypercapnic,Respiratory Failure, Hypoxemic,Respiratory Failures
D005283 Fentanyl A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078) Phentanyl,Duragesic,Durogesic,Fentanest,Fentanyl Citrate,Fentora,R-4263,Sublimaze,Transmucosal Oral Fentanyl Citrate,R 4263,R4263
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013745 Tetanus Toxoid Tetanus Vaccine,Toxoid, Tetanus,Vaccine, Tetanus
D014614 Vaccines, Synthetic Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified. Antigens, Synthetic,Chemical Vaccine,Chemical Vaccines,Immunogens, Synthetic,Molecular Vaccine,Molecular Vaccines,Recombinant Vaccine,Semisynthetic Vaccine,Semisynthetic Vaccines,Synthetic Antigen,Synthetic Vaccine,Synthetic Vaccines,Vaccines, Recombinant,Synthetic Antigens,Synthetic Immunogens,Vaccines, Chemical,Vaccines, Molecular,Vaccines, Semisynthetic,Antigen, Synthetic,Recombinant Vaccines,Vaccine, Chemical,Vaccine, Molecular,Vaccine, Recombinant,Vaccine, Semisynthetic,Vaccine, Synthetic
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018796 Immunoconjugates Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers. Antibody Drug Conjugate,Antibody-Drug Conjugate,Radioimmunoconjugates,Antibody-Drug Conjugates,Immunoconjugate,Radioimmunoconjugate,Antibody Drug Conjugates,Conjugate, Antibody Drug,Conjugate, Antibody-Drug,Conjugates, Antibody-Drug,Drug Conjugate, Antibody

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