Vaccines against Drugs of Abuse

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 7257

Special Issue Editors


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Guest Editor
Adjuvants and Formulation Section, Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Interests: opioid vaccines; adjuvants; immunology

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Guest Editor
Molecular Targets and Medications Discovery Branch (MTMDB), National Institute on Drug Abuse (NIDA), and National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA
Interests: opioid vaccines; hapten design;synthetic chemistry

Special Issue Information

Dear Colleagues,

Substance use disorders (SUDs) continue to be a serious global concern with profound effects on public health. According to the World Health Organization (WHO), about 35 million people are estimated to be affected by SUDs and about 0.5 million deaths annually are attributable to illicit drug use. There are still very few available treatments for SUDs. Vaccines against drugs of abuse have the potential to save countless lives and alleviate many of the socioeconomic burdens associated with SUDs. They act by inducing the immune system to produce antibodies that target the drugs in the periphery and prevent them from reaching the brain and acting on the target receptors. However, the development of vaccines against drugs of abuse, which are small molecules and do not themselves elicit an immune response, pose many challenges. One of the challenges is the choice of hapten, a small-molecule mimic of the abused drug. The structure of that hapten must be configured to engage not only the specific abused drug but also its metabolites and structural relatives. It is also important that the vaccine does not interact with approved medications for SUDs. There is an urgent need to develop novel treatments for SUDs, and vaccines against drugs of abuse may represent a clinically viable strategy.

We are pleased to invite you to contribute to a Special Issue of Vaccines designated Vaccines Against Drugs of Abuse.

The goal of this Issue is to discuss recent advances in the development of vaccines against drugs of abuse, including vaccines against opioids, cocaine, amphetamines, nicotine, and synthetic cannabinoids and so on.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the design and formulation of vaccines against drugs of abuse, carriers, adjuvants, and hapten designs.

We look forward to receiving your contributions.

Dr. Gary R. Matyas
Dr. Agnieszka Sulima
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vaccines
  • drugs of abuse
  • opioids
  • cocaine
  • amphetamines
  • nicotine
  • synthetic cannabinoids
  • carriers
  • adjuvants
  • haptens

Published Papers (3 papers)

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Research

8 pages, 381 KiB  
Article
A Clinical Trial of Entolimod a TLR-5 Adjuvant for Vaccines Using Diphtheria or Tetanus as Carrier Proteins
by Thomas R. Kosten, Coreen B. Domingo, Colin N. Haile and David A. Nielsen
Vaccines 2022, 10(10), 1592; https://doi.org/10.3390/vaccines10101592 - 22 Sep 2022
Cited by 1 | Viewed by 1327
Abstract
Anti-drug vaccines previously failed clinical trials because they did not provide a sufficient titer or duration of antibodies (AB), but new adjuvants enhance both AB titers and efficacy duration. This clinical trial assessed AB titers after a single booster of commercial tetanus-diphtheria (Td) [...] Read more.
Anti-drug vaccines previously failed clinical trials because they did not provide a sufficient titer or duration of antibodies (AB), but new adjuvants enhance both AB titers and efficacy duration. This clinical trial assessed AB titers after a single booster of commercial tetanus-diphtheria (Td) vaccine in 40 males randomized as 15 to Td alone and 25 to Td combined with the TLR5 adjuvant, Entolimod (Ent). Ent significantly increased ABs against diphtheria (DPT) (0.46 vs. 0.29 IU/mL increase; n = 40, p < 0.05), but against tetanus (TT) only if baseline TT AB was below 3 IU/mL (3.1 vs. 2.1 IU/mL; n = 20; p < 0.05). These 20 participants also showed a two-fold increase in anti-TT AB titer more often when given Ent than non-Ent (33% vs. 82%) (p < 0.03). Anti-Ent AB was low and appeared unlikely to reduce Ent efficacy after repeated Ent administration. Medical safety was excellent, and a TLR5 missense polymorphism reduced anti-DPT AB production, but Ent increased anti-DPT AB titers to levels induced in subjects with genetically “normal” TRL5 functioning. Further clinical testing of TLR5 adjuvants like Ent seems warranted for anti-drug vaccines. Full article
(This article belongs to the Special Issue Vaccines against Drugs of Abuse)
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15 pages, 990 KiB  
Article
Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine
by Colin N. Haile, Kurt J. Varner, Xia Huijing, Reetakshi Arora, Frank M. Orson, Thomas R. Kosten and Therese A. Kosten
Vaccines 2022, 10(9), 1508; https://doi.org/10.3390/vaccines10091508 - 9 Sep 2022
Cited by 4 | Viewed by 2369
Abstract
Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated [...] Read more.
Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod. Methods: Mice were vaccinated (0, 3, 6 weeks) with TT-SMA+alum and various doses of entolimod to determine an optimal dose for enhancing immunogenicity against MA. Functional effects were then assessed using MA-induced locomotor activation in mice. Experiments using passive immunization of antibodies generated by the vaccine tested its ability to attenuate MA-induced cardiovascular effects and alter the reinforcing effects of MA in an MA-induced reinstatement of a drug seeking model of relapse in male and female rats. Results: Antibody levels peaked at 10 weeks following vaccination with TT-SMA+alum combined with entolimod (1, 3 and 10 μg). MA-induced locomotor activation was significantly attenuated in vaccinated vs. unvaccinated mice and antibody levels significantly correlated with ambulation levels. Passive immunization decreased mean arterial pressure following MA dosing in rats of both sexes but did not alter heart rate. Passive immunization also attenuated the ability of MA to reinstate extinguished drug-seeking behavior in male and female rats. Results support further development of this vaccine for relapse prevention for individuals with MUD. Full article
(This article belongs to the Special Issue Vaccines against Drugs of Abuse)
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13 pages, 1129 KiB  
Article
Development of Cross-Reactive Antibodies for the Identification and Treatment of Synthetic Cannabinoid Receptor Agonist Toxicity
by Adam Worob and Cody J. Wenthur
Vaccines 2022, 10(8), 1253; https://doi.org/10.3390/vaccines10081253 - 4 Aug 2022
Cited by 1 | Viewed by 3099
Abstract
Synthetic cannabinoid receptor agonists (SCRAs) are compounds that mimic the pharmacology of the psychoactive components in cannabis. These compounds are structurally diverse, inexpensive, commercially available, and difficult to identify with modern analytical methods, making them highly accessible for recreational use. Suspected SCRA toxicity, [...] Read more.
Synthetic cannabinoid receptor agonists (SCRAs) are compounds that mimic the pharmacology of the psychoactive components in cannabis. These compounds are structurally diverse, inexpensive, commercially available, and difficult to identify with modern analytical methods, making them highly accessible for recreational use. Suspected SCRA toxicity, which can present with a breadth of cardiovascular, gastrointestinal, and neurological disturbances, is currently addressed through symptom management followed by a toxicological screening that often occurs long after patient discharge. Here, we report the development of four cross-reactive anti-SCRA bioconjugate vaccines as a platform for developing improved diagnostic and therapeutic interventions against SCRA intoxication, using SCRA-resembling small molecule haptens that combine common subregional motifs occurring within and across different generations of SCRA molecules. Using a combination of multiplexed competitive ELISA screening and chemoinformatic analyses, it was found that the antibodies resulting from vaccination with these bioconjugates demonstrated their ability to detect multiple SCRAs with a Tanimoto minimum common structure score of 0.6 or greater, at concentrations below 8 ng/mL. The scope of SCRAs detectable using these haptens was found to include both bioisosteric and non-bioisosteric variants within the core and tail subregions, as well as SCRAs bearing valine-like head subregions, which are not addressed by commercially available ELISA screening approaches. Vaccination with these bioconjugates was also found to prevent the changes in locomotion and body temperature that were induced by a panel of SCRAs at doses of 1 and 3 mg/kg. Further refinement of this genericized hapten design and cross-reactivity-prioritizing approach may enable the rapid detection of otherwise cryptic SCRAs that arise during overdose outbreaks, and could ultimately lead to identification of monoclonal antibody species applicable for overdose reversal. Full article
(This article belongs to the Special Issue Vaccines against Drugs of Abuse)
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