Induction of the Activation of Immunity Against Opioids and Mycobacterium tuberculosis by a Chimeric Vaccine

Abstract

Drug addiction has dire consequences for individuals and significantly threatens public well- being. Presently, opioid substitution therapy (OST) relies on buprenorphine, a morphine agonist, to address opioid dependency. However, a risk exists of patients developing dependence on the treatment drug. Naloxone is employed in OST as a carrier for buprenorphine. While naloxone competes with opioids for binding, it can result in various adverse effects, including cardiovascular complications, brain tissue damage, and neurological disorders. Numerous studies have indicated a higher prevalence of tuberculosis (TB) infection among individuals struggling with drug addiction. Opioids contribute to immunosuppression, rendering individuals more susceptible to TB. Hence, it is crucial to explore alternative therapies for opioid addiction. Vaccines have played a vital role in eradicating debilitating diseases like poliomyelitis, smallpox, and measles. Similarly, vaccines can serve as a powerful tool in mitigating the effects of opioids. We utilised nanotechnology and created a novel vaccine displaying morphine and Pam3Cys (TLR-2 agonist) on the surface of Acr1 nanoparticles (MAPNV). Acr1, an immunodominant antigen of Mycobacterium tuberculosis (Mtb), holds potential as a vaccine candidate against TB. The MAPNV vaccine demonstrated self-adjuvant properties and stimulated the proliferation and differentiation of morphine-specific B cells and Acr1-reactive CD4 T cells. Vaccination induced the production of high-affinity anti-morphine antibodies, which effectively eliminated morphine from the bloodstream and brain of the animals. Additionally, a downregulation in the expression of addiction-associated OPRM and dopamine genes was observed. This suggests the vaccine may prevent morphine from binding to opioid receptors and reduce its addictive effects. Moreover, a significant increase in the pool of memory CD4 T cells and B cells indicates the long-lasting impact of the vaccine. Generating morphine-reactive B cells and Acr1-specific CD4 T cells further highlights the vaccine's potential to confer immunity against morphine and Mtb. In the future, MAPNV holds promise to protect against morphine addiction and TB infection.