(641b) Antigen–Loaded Polymer–Hapten Nanoparticles to Induce Small Molecule-Specific Antibodies

The opioid epidemic represents a global health crisis with rising opioid use disorder (OUD) and fatal overdoses. Opioid vaccines are a desirable category of next-generation therapy, but opioids alone are not immunogenic when delivered to the host due to their low molecular weight. Research has shown that opioids can be used as ‘haptens,’ i.e. molecules that can induce immune responses when they are chemically conjugated to a carrier protein or when conjugated to the surface of particles such as virus-like particles (VLPs) or other nanoparticles (NP). Achieving a high hapten surface density and hapten-specific antibody induction remains a challenge for the protein-hapten approach, though. In this study, we prepared and evaluated a proof-of-concept small molecule vaccine by encapsulating ovalbumin as an immunogenic CD4+ T cell helper protein into core-shell nanocarriers with a shell of poly(caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) polymer chains terminated with a model small molecule hapten, trinitrophenyl (TNP). A combination of unconjugated PCL-b-PEG and PCL-b-PEG-TNP was used to achieve different levels of TNP surface coverage. The size and polydispersity index (PDI) of the nanoparticles (118.9 – 139.2 nm and 0.17 – 0.23, respectively) remain consistent across different percentages of surface polymer chains terminated with TNP (0%, 1%, 10%, 50%, and 100%). The immunogenicity of the nanoparticle vaccines after intramuscular immunization in BALB/c mice was evaluated for the induction of OVA-specific and TNP-specific antibodies. Increasing the surface coverage of TNP from 0% to 100% of surface polymer chains induced elevated serum OVA-TNP-, OVA-, and TNP-specific IgG antibodies in mice, with the TNP-specific antibody response induced by OVA-TNP nanoparticles dependent on the degree of TNP surface coverage. This demonstrates proof of principle for the use of polymeric NPs as alternative hapten carriers to hapten-protein conjugates; future work will evaluate both the neutralizing efficiency of the TNP-specific antibodies induced by NPs versus protein-hapten conjugates, and the possibility of co-loading adjuvants into the NP core for improved immune response.