The continuing search for an addiction vaccine M. Heval Ozgen a,⇑ , Stuart Blume b a Parnassia Psychiatric Institute and Addiction Research Center (PARC), Interculturel Psychiatry (i-psy), Parnassia Academy, The Hague, the Netherlands b Department of Anthropology, University of Amsterdam, Amsterdam, the Netherlands article info Article history: Received 29 September 2018 Received in revised form 27 April 2019 Accepted 24 June 2019 Available online xxxx Keywords: Addiction Synthetic opioids Metabolites Unconventional carriers Behavioural endpoints Ethics abstract Inspired by advances in immunology, in the 1970s scientists began to study the possibilities of mobilizing the human immune system against intruders other than pathogenic viruses and bacteria. In 1972 the suggestion was first made that it might be possible to provoke immunity to narcotic dependence. Because molecules of narcotics such as heroin and cocaine are too small to stimulate an immune response, researchers sought ways of coupling them to immunogenic proteins. The substances they developed soon became known as addiction vaccines. However, despite fifty years of research, and despite the growing problem of addiction, no vaccine against heroin, cocaine, methamphetamine or nico- tine addiction has yet been licensed for clinical use. This paper reviews the history of addiction vaccinol- ogy, seeks to explain the unique appeal of a vaccinological approach to addiction, and argues for broad discussion of how such vaccines should ultimately be used. Ó 2019 Published by Elsevier Ltd. 1. Introduction From hesitant beginnings more than a century ago, vaccination against infectious diseases has become a keystone of today’s global health. Its prime objective is of course to save lives. Vaccines have saved countless lives, and despite 19th century resistance to com- pulsory smallpox vaccination, and despite today’s ‘vaccine hesi- tancy’ [1], most people accept that this is what it does. Moreover, when experts warn of an impending epidemic, hopes are immedi- ately pinned on a rapidly-to-be-developed vaccine against Ebola for example, or Zika. The spate of dystopian films and TV series indicate how this faith in vaccination as the principal source of hope, of salvation, has become embedded in popular culture [2]. This may be particularly true of the United States, with its distinc- tive faith in the possibility of technological solutions to problems of health and society [3,4]. The existence of a new vaccine does not in itself determine how it will be used. Both with rubella and more recently with HPV the objective of vaccination was changed from protecting individual girls to halting circulation of the virus. When a vaccine against hepatitis B became available some countries limited vaccination to defined risk groups, because the disease was rare and the vac- cine expensive. However, faced with a recommendation from the WHO, and with the argument that demarcating risk-groups was problematic, the policy was largely abandoned. Understanding of how precisely vaccines work grew more slowly than their use in practice. However developments in the field of immunology led to the realization that it should be possible to mobilize the immune system in tackling intruders other than infectious pathogens. Researchers then began to study the possibil- ities of creating vaccines against a variety of very different condi- tions. These include breast cancer [5], conception [6], Alzheimer’s disease [7], obesity [8], and addiction. Building on developments both in immunology and in neuro- chemistry, in the 1970s scientists began to study ways in which molecules of addictive substances such as cocaine, heroin and methamphetamines, as well as nicotine could be modified so as to elicit an immune response. The substances that they synthesized soon became known as addiction vaccines. In this paper we first review the history of attempts at developing addiction vaccines, and the challenges they face. Few candidate vaccines have entered Phase III trials. Though none has as yet proven successful research- ers are undeterred. This study aims to examine what lies behind the continuing appeal of an addiction vaccine, and suggest that consideration should be given to the ways in which these vaccines might eventually be used. 2. History of addiction vaccinology At the start of the 1970s illegal drug use in the United States was rising. There were fears that returning Vietnam veterans https://doi.org/10.1016/j.vaccine.2019.06.074 0264-410X/Ó 2019 Published by Elsevier Ltd. ⇑ Corresponding author at: Parnassia Addiction Research Centre, Parnassia Academy, Kiwistraat 43, 2552 DH Den Haag, the Netherlands. E-mail address: m.h.ozgen@parnassiagroep.nl (M.H. Ozgen). Vaccine xxx (xxxx) xxx Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Please cite this article as: M. H. Ozgen and S. Blume, The continuing search for an addiction vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2019.06.074