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.
