Opioid addiction and overdose related deaths have increased at alarming rate. Although naloxone offers an overdose rescue treatment but does not provide lasting protection. Recently, vaccines that aim to elicit opioid-specific antibodies (Abs) that bind opioids, and prevent them from passing into the brain and other organs, have emerged as possible passive interventions for opioid abuse. To induce an anti-opioid Ab response, current experimental vaccines are comprised of adjuvants admixed with an antigen composed of monomeric opioids covalently attached to a carrier protein. This design allows for the activation of opioid-specific B cells via adjuvant-mediated immune activation, crosslinking of opioid-specific B cell receptors (BCRs), and activation of T cell help through peptides derived from the carrier protein. We hypothesized that a polymeric conjugate vaccine composed of a carrier protein modified with polymers decorated with opioids and a B cell adjuvant would enhance BCR crosslinking and localize immune stimulation to B cells, resulting in enhanced B cell activation. To generate a polymeric fentanyl vaccine, we synthesized block copolymer, termed p(TLR-b-Fent), bearing a ligand for toll-like receptors 7 & 8 (TLR7/8) (i.e., R848) and fentanyl then conjugated p(TLR7/8-b-Fent) to the carrier protein ovalbumin (OVA) . Here, we demonstrate that OVA-p(TLR7/8-b-Fent) offers an improved anti-fentanyl IgG antibody response with superior avidity against fentanyl than a state-of-the-art monomeric vaccine. Given the modularity of our approach we anticipate that our polymeric vaccine can be easily adapted to protect against numerous other opioids and infectious diseases.
