Pre-clinical characterization of virus-like particles as a platform for nanovaccines against heroin and oxycodone

Opioid use disorder (OUD) and drug-related overdoses continue to pose a major public health challenge in the United States, Canada, Europe and other countries worldwide. While effective treatments for OUD such as methadone, buprenorphine, and naltrexone, as well as overdose reversal medications such as naloxone and nalmefene, are available, access to medication assisted treatments (MATs) remains limited. This underscores the need for the development and implementation of new therapeutic strategies. As a potential strategy to address the shortcomings of current pharmacotherapies and complement their use, vaccines targeting opioids offer an additional treatment for OUD and prevention of overdose. After active immunization, vaccines trigger an immune response that generate drug-specific polyclonal antibodies that sequester the target drug in the bloodstream and organs, preventing from crossing the blood brain barrier (BBB), thereby reducing the concentration of unbound (free) drug in the brain, ultimately weakening its pharmacological and behavioral effects. Striving for more effective vaccines, a wealth of literature explored how various vaccine components can be optimized to enhance the quality and quantity of the immune response. In this landscape, drug conjugate vaccines containing virus like particles (VLP) against nicotine and opioids have been reported. Hence, this study explores use of VLPs as alternative carriers to the candidate vaccines against heroin (M-sKLH) and oxycodone (OXY-sKLH) currently in either late-stage development or in clinical trials (NCT04458545) respectively. Both the lead oxycodone (OXY) and morphine (M) haptens have been scaled up under GMP conditions, the safety of their conjugates (OXY-sKLH and M-sKLH) have been tested in GLP toxicology studies and have been reviewed by the Food and Drug Administration (FDA) in either Investigational New Drug (IND) or pre-IND meetings. The current experiments aim to test whether VLP-based vaccines can elicit an effective antibody response to mitigate opioid effects.