Vaccines against Drug Abuse—Are We There Yet?

Abstract

Background: Drug abuse is a worldwide problem that is detrimental to public health. The potential for drug abuse extends to both legal and illicit drugs. Drawbacks associated with current treatments include limited effectiveness, potential side effects and, in some instances, the absence of or concerns with approved therapy options. A significant amount of clinical research has been conducted investigating immunotherapy as a treatment option against drug abuse. Vaccines against drug abuse have been the main area of research, and are the focus of this review. Methods: An extensive search using “EBSCOhost (Multiple database collection)” with all 28 databases enabled (including “Academic Search Ultimate”, “CINAHL Plus with Full Text”, and MEDLINE), interrogation of the ClinicalTrials.gov website, and searches of individual clinical trial registration numbers, was performed in February and March of 2022. This search extended to references within the obtained articles. Results: A total of 23 registered clinical trials for treating drug abuse were identified: 15 for treatment of nicotine abuse (all vaccine-based trials), 6 against cocaine abuse (4 were vaccine-based trials and 2 were metabolic-enzyme-based trials), 1 against methamphetamine abuse (a monoclonal-antibody-based trial), and 1 multivalent opioid treatment (vaccine-based trial). As indicated on the ClinicalTrials.gov website (Home—ClinicalTrials.gov), the status of all but two of these trials was “Completed”. Phase 3 clinical trials were completed only for vaccine treatments against nicotine abuse. Conclusion: Evidence in the form of efficacy data indicates that vaccines are not an option for treating nicotine or cocaine abuse. Efficacy data are yet to be obtained through completion of clinical trials for vaccines against opioid abuse. These findings align with the absence of regulatory approval for any of these treatments. This review further highlights the need for novel treatment strategies in instances where patients do not respond to current treatments, and while the search for efficacious vaccine-based treatments continues.

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

“…Passive vaccination, where the patient receives drug-specific engineered or monoclonal antibodies, permits the treatment of time-sensitive drug-use scenarios, such as rapid detoxification. Passive vaccination only lasts a few weeks or months since the antibodies are not generated through the patient’s own immune system and so lack the memory response properties provided through active vaccination. − …”

“…Following successful pre-clinical studies for GNC conjugated to CTB (TA-CD) and dAd5GNE (Table 1), both vaccines have undergone phase 2 and phase 3 clinical trials, namely TA-CD and dAd5GNE (Table 2). 33 TA-CD and dAd5GNE vaccines are cocaine hapten analogues (GNC and GNE, respectively; Figure 3) chemically conjugated to a recombinant carrier protein administered with an additional adjuvant. Both TA-CD and dAd5GNE vaccines were designed to elicit cocaine-specific IgG antibodies following vaccination with the aim to bind free cocaine and prevent it from crossing the blood−brain barrier into the brain (Figure 2).…”

“…By combining an antigenic carrier (e.g., protein) with cocaine, vaccination stimulated the production of anti-cocaine antibodies that bind with the cocaine molecule to form a complex that was too large to cross the blood–brain barrier, reducing the euphoric high and rewarding effects of cocaine use (Figure ). − Immunity to any disease was produced through the presence of antibodies, where antibodies are disease-specific proteins produced by the body to destroy disease-carrying organisms. Immunity against a disease works by two mechanisms, active or passive immunity, with the development of anti-cocaine vaccines or monoclonal antibodies falling under these two categories, respectively (Figure ).…”

“…Immunity against a disease works by two mechanisms, active or passive immunity, with the development of anti-cocaine vaccines or monoclonal antibodies falling under these two categories, respectively (Figure ). − Active vaccination following immunization with a drug-specific antigen/hapten confers long-term (or sometimes lifetime) protection against addictive behaviors triggered when exposed to the drug triggering the immune system to produce antibodies. Passive vaccination, where the patient receives drug-specific engineered or monoclonal antibodies, permits the treatment of time-sensitive drug-use scenarios, such as rapid detoxification.…”

Evaluation of Multi-target Drugs on the Cocaine-induced Locomotor Sensitization in Rats

“…However, the results of these clinical trials remain inconsistent and the clinical application of these drugs is limited, given that the studies report a high attrition rate, relapse, morbidity, and mortality (Truong and Kosten, 2022;Gaines et al, 2022;Bloom and Bushell, 2022). Thus, despite many efforts, no drug approved by the Food and Drug Administration (FDA) has yet been safe and effective in treating CUD (Chan et al, 2019;Buchholz and Saxon, 2019).…”