Vaccines to combat the opioid crisis

Olson, Margaret E.; Janda, Kim D.

doi:10.15252/embr.201745322

Cited by 19 publications

(11 citation statements)

References 10 publications

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“…Active immunization is an emerging approach that might be useful as a medication for opioid use disorders. 2 , 24 − 26 Immunization induces an immune response against the opioid immunogen, and the antibodies produced can sequester these drugs in the blood. 24 , 25 This impedes the ability of opioids to permeate the blood–brain barrier and prevent their access to receptors in the brain.…”

Section: Introductionmentioning

confidence: 99%

Novel Vaccine That Blunts Fentanyl Effects and Sequesters Ultrapotent Fentanyl Analogues

et al. 2020

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Active immunization is an emerging potential modality to combat fatal overdose amid the opioid epidemic. In this study, we described the design, synthesis, formulation, and animal testing of an efficacious vaccine against fentanyl. The vaccine formulation is composed of a novel fentanyl hapten conjugated to tetanus toxoid (TT) and adjuvanted with liposomes containing monophosphoryl lipid A adsorbed on aluminum hydroxide. The linker and hapten N -phenyl- N -(1-(4-(3-(tritylthio)propanamido)phenethyl)piperidin-4-yl)propionamide were conjugated sequentially to TT using amine- N -hydroxysuccinimide-ester and thiol–maleimide reaction chemistries, respectively. Conjugation was facile, efficient, and reproducible with a protein recovery of >98% and a hapten density of 30–35 per carrier protein molecule. In mice, immunization induced high and robust antibody endpoint titers in the order of >10 6 against the hapten. The antisera bound fentanyl, carfentanil, cyclopropyl fentanyl, para -fluorofentanyl, and furanyl fentanyl in vitro with antibody-drug dissociation constants in the range of 0.36–4.66 nM. No cross-reactivity to naloxone, naltrexone, methadone, or buprenorphine was observed. In vivo , immunization shifted the antinociceptive dose–response curve of fentanyl to higher doses. Collectively, these preclinical results showcased the desired traits of a potential vaccine against fentanyl and demonstrated the feasibility of immunization to combat fentanyl-induced effects.

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Section: Introductionmentioning

confidence: 99%

Novel Vaccine That Blunts Fentanyl Effects and Sequesters Ultrapotent Fentanyl Analogues

et al. 2020

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“…The National Science Foundation (NSF), for example, estimates about 2.3 million publications worldwide yearly, but this estimate does include some non-medical engineering publications [27]. Another approximation cited in the literature indicates roughly 2.5 million annual publications [20, 28]. Other calculations, based on SCOPUS (Elsevier’s abstract and citation database) and Web of Science (Clarivate Analytics citation indexing service), have concluded there are about 2.2 million yearly research publications [29].…”

Section: Methodsmentioning

confidence: 99%

“…While this certainly promotes some uniformity, it does not fully address the more granular and highly variable formatting prerequisites for manuscript publications that, even today, are common with publishers. With an average manuscript submission rejection rate of about 62%, much higher at top tier journals, this delay affects the majority of submissions and could have substantial cumulative effect [20]. This is particularly relevant as it seems there are some trends, at least for some of the most selective journals, which would further increase the delays and resources required to ultimately publish.…”

Section: Introductionmentioning

confidence: 99%

The high resource impact of reformatting requirements for scientific papers

et al. 2019

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BackgroundMost research manuscripts are not accepted for publication on first submission. A major part of the resubmission process is reformatting to another journal’s specific requirements, a process separate from revising the scientific content. There has been little research to understand the magnitude of the burden imposed by the current resubmission process.MethodsWe analyzed original research article submission requirements from twelve randomly selected journals in each of eight scientific and clinical focus areas from the InCites Journal Citation Reports database. From the 96 journals selected, we randomly identified three recently published manuscripts and sent surveys to those first and/or corresponding authors (288 total) to solicit information on time spent reformatting resubmissions and opinions on the process.FindingsThere was significant variation in manuscript submission requirements for journals within the same scientific focus and only 4% of journals offered a fully format-free initial submission. Of 203 authors responding (71.5% response rate), only 11.8% expressed satisfaction with the resubmission process and 91% desired reforming the current system. Time spent on reformatting delays most publications by at least two weeks and by over three months in about 20% of manuscripts. The effort to comply with submission requirements has significant global economic burden, estimated at over $1.1 billion dollars annually when accounting for a research team’s time.InterpretationWe demonstrate that there is significant resource utilization associated with resubmitting manuscripts, heretofore not properly quantified. The vast majority of authors are not satisfied with the current process. Addressing these issues by reconciling reformatting requirements among journals or adopting a universal format-free initial submission policy would help resolve a major subject for the scientific research community and provide more efficient dissemination of findings.

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“…Hurd et al [128] examined the strategies that targeted specific genetic and epigenetic factors, along with novel nonopioid medications, which showed promising therapeutic potential for the prevention of opioid abuse. Another study by Olson and Janda [129] put forward the novel idea of opioid vaccines for the prevention of opioid abuse.…”

Section: Prevention Strategies For Opioid Abusementioning

confidence: 99%

Risk Factors and Prevention Strategies for Postoperative Opioid Abuse

Zhao

Chen

Feng

et al. 2019

Pain Research and Management

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Worldwide, 80% of patients who undergo surgery receive opioid analgesics as the fundamental agent for pain relief. However, the irrational use of opioids leads to excessive drug dependence and drug abuse, resulting in an increased mortality rate and huge economic loss. The crisis of opioid overuse remains a great challenge. In this review, we summarize several key factors in opioid abuse, including race, region, income, genetic factors, age and gender, smoking and alcohol abuse, history of chronic pain and analgesic drug abuse, surgery, neuropsychiatric illness, depression and antidepressant use, human factors, national policies, hospital regulations, and health insurance under treatment of pain. Furthermore, we present several prevention strategies, such as perioperative measures, opioid substitutes, treatment of the primary illness, emotional regulation, use of opioid antagonists, efforts of the state, hospitals, doctors and pharmacy benefit managers, gene therapy, and vaccines. Greater understanding and better assessment are required of the risks associated with opioid abuse to ensure the safety and analgesic effects of pain treatment after surgery.

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Vaccines to combat the opioid crisis

Abstract: Novel vaccines against substances of abuse generate a strong antibody response that prevents the drug from entering the brain. These could become a safe and efficient tool to combat a growing crisis of opioid abuse.

Cited by 19 publications

References 10 publications

Novel Vaccine That Blunts Fentanyl Effects and Sequesters Ultrapotent Fentanyl Analogues

Novel Vaccine That Blunts Fentanyl Effects and Sequesters Ultrapotent Fentanyl Analogues

The high resource impact of reformatting requirements for scientific papers

Risk Factors and Prevention Strategies for Postoperative Opioid Abuse

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