Monoclonal antibodies (mAbs) and vaccines have been proposed as medical countermeasures to treat opioid use disorder (OUD) and prevent opioid overdose. In contrast to current pharmacotherapies (e.g., methadone, buprenorphine, naltrexone, and naloxone) for OUD and overdose, which target brain opioid receptors, mAbs and vaccine-generated polyclonal antibodies sequester the target opioid in the serum and reduce drug distribution to the brain. Furthermore, mAbs offer several potential clinical benefits over approved medications, such as longer serum half-life, higher selectivity, reduced side effects, and no abuse liability. Using magnetic enrichment to isolate opioid- specific B cell lymphocytes prior to fusion with myeloma partners, this study identified a series of murine hybridoma cell lines expressing mAbs with high affinity for opioids of clinical interest, including oxycodone, heroin and its active metabolites, and fentanyl. In mice, passive immunization with lead mAbs against oxycodone, heroin, and fentanyl reduced drug-induced antinociception and the distribution of the target opioid to the brain. Inmice and rats, mAb pretreatment reduced fentanyl-induced respiratory depression and bradycardia, two risk factors for opioid-related overdose fatality. Overall, these results support use of mAbs to counteract toxic effects of opioids and other chemical threats. SIGNIFICANCE STATEMENT The incidence of fatal overdoses due to the widespread access to heroin, prescription opioids, and fentanyl suggests that current Food and Drug Administration-approved countermeasures are not sufficient to mitigate the opioid epidemic. Monoclonal antibodies (mAbs) may provide acute protection from overdose by binding to circulating opioids in serum. Use of mAbs prophylactically, or after exposure in combination with naloxone, may reduce hospitalization and increase survival.
机构:
Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Peking Univ, Beijing Key Lab Drug Dependence, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Han, Ying
;
Yan, Wei
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h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Yan, Wei
;
Zheng, Yongbo
论文数: 0引用数: 0
h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Zheng, Yongbo
;
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机构:
Khan, Muhammad Zahid
;
Yuan, Kai
论文数: 0引用数: 0
h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Yuan, Kai
;
Lu, Lin
论文数: 0引用数: 0
h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R China
Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Ho, Irvin Y.
;
Bunker, Jeffrey J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Pathol, 929 E 57th St W503S, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Bunker, Jeffrey J.
;
Erickson, Steven A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Pathol, 929 E 57th St W503S, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Erickson, Steven A.
;
Neu, Karlynn E.
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h-index: 0
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Neu, Karlynn E.
;
Huang, Min
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h-index: 0
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Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Huang, Min
;
Cortese, Mario
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机构:
Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Cortese, Mario
;
Pulendran, Bali
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机构:
Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Pulendran, Bali
;
Wilson, Patrick C.
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h-index: 0
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Laudenbach, Megan
;
Baruffaldi, Federico
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h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Baruffaldi, Federico
;
Robinson, Christine
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h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Robinson, Christine
;
Carter, Philipp
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Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Carter, Philipp
;
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机构:
Seelig, Davis
;
Baehr, Carly
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Laudenbach, Megan
;
Baruffaldi, Federico
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Univ Milan, Fac Sci Farmaco, I-20133 Milan, ItalyMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Baruffaldi, Federico
;
Vervacke, Jeffrey S.
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机构:
Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Vervacke, Jeffrey S.
;
Distefano, Mark D.
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Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Distefano, Mark D.
;
Titcombe, Philip J.
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Univ Minnesota, Ctr Immunol, Dept Med, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Titcombe, Philip J.
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Mueller, Daniel L.
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Univ Minnesota, Ctr Immunol, Dept Med, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Mueller, Daniel L.
;
Tubo, Noah J.
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h-index: 0
机构:
Univ Minnesota, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Tubo, Noah J.
;
Griffith, Thomas S.
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h-index: 0
机构:
Univ Minnesota, Ctr Immunol, Dept Urol, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
机构:
Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Peking Univ, Beijing Key Lab Drug Dependence, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Han, Ying
;
Yan, Wei
论文数: 0引用数: 0
h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Yan, Wei
;
Zheng, Yongbo
论文数: 0引用数: 0
h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Zheng, Yongbo
;
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机构:
Khan, Muhammad Zahid
;
Yuan, Kai
论文数: 0引用数: 0
h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
Yuan, Kai
;
Lu, Lin
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h-index: 0
机构:
Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Inst Mental Hlth,NHC Key Lab Mental Hlth, Beijing 100191, Peoples R China
Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R ChinaPeking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Ho, Irvin Y.
;
Bunker, Jeffrey J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Pathol, 929 E 57th St W503S, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Bunker, Jeffrey J.
;
Erickson, Steven A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Pathol, 929 E 57th St W503S, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Erickson, Steven A.
;
Neu, Karlynn E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Neu, Karlynn E.
;
Huang, Min
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Huang, Min
;
Cortese, Mario
论文数: 0引用数: 0
h-index: 0
机构:
Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Cortese, Mario
;
Pulendran, Bali
论文数: 0引用数: 0
h-index: 0
机构:
Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Pulendran, Bali
;
Wilson, Patrick C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
Univ Chicago, Comm Immunol, Chicago, IL 60637 USAUniv Chicago, Rheumatol Sect, Dept Med, Gwen Knapp Ctr Lupus & Immunol Res, 924 E 57th St R422, Chicago, IL 60637 USA
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Laudenbach, Megan
;
Baruffaldi, Federico
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Baruffaldi, Federico
;
Robinson, Christine
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Robinson, Christine
;
Carter, Philipp
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Carter, Philipp
;
论文数: 引用数:
h-index:
机构:
Seelig, Davis
;
Baehr, Carly
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55404 USA
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Laudenbach, Megan
;
Baruffaldi, Federico
论文数: 0引用数: 0
h-index: 0
机构:
Minneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Univ Milan, Fac Sci Farmaco, I-20133 Milan, ItalyMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Baruffaldi, Federico
;
Vervacke, Jeffrey S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Vervacke, Jeffrey S.
;
Distefano, Mark D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Distefano, Mark D.
;
Titcombe, Philip J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Minnesota, Ctr Immunol, Dept Med, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Titcombe, Philip J.
;
Mueller, Daniel L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Minnesota, Ctr Immunol, Dept Med, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Mueller, Daniel L.
;
Tubo, Noah J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Minnesota, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA
Tubo, Noah J.
;
Griffith, Thomas S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Minnesota, Ctr Immunol, Dept Urol, Minneapolis, MN 55455 USAMinneapolis Med Res Fdn Inc, Minneapolis, MN 55415 USA