Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

Vijayan, Veena; Mohapatra, Adityanarayan; Uthaman, Saji; Park, In-Kyu

Melittin is a linear cytosolic peptide that is secreted from honey bee venom. If injected into an animal body, it causes pain sensation, owing to pore formation in epithelial cells. This cationic peptide is responsible for cell membrane lysis caused by high interaction with negatively charged phospholipids, and it inhibits ion transportation into cells. The current strategies to fight against melittin are based on toxoid vaccination. The elimination of toxicity in pore-forming toxins and the preservation of the immunity epitope is a considerable challenge for researchers. Biomimetic nanovaccines are the best alternatives for the delivery of these toxins as a suitable toxoid vaccine, since they maintain the antigenic activities of the native toxin to induce an immune response in the body. The RBC membrane-coated NP was used as a suitable carrier to anchor the staphylococcal a-hemolysin (Hla) model toxin towards non-disruptive nanotoxoid formation [25] . Nanotoxoid vaccination stimulated the host body immunity and eliminated the toxins through antigen-presenting mechanisms. Kang et al. [141] reported that the nanotoxoid formation method might be a promising approach for pore-forming toxins (PFTs) vaccines. The synthetic PDA NP can efficiently neutralize melittin to reduce the toxicity of melittin. The interaction of polydiacetylene (PDA) NP with melittin was mediated by both hydrophobic and electrostatic interactions. Melittin-loaded PDA NP was used as a nanotoxoid vaccination to enhance immune activity against melittin. PDA-melittin demonstrated 70% cell viability in DCs, whereas free melittin showed 90% cell apoptosis [141] . This biomimetic nanovaccine maintained the antigenic determinant of the melittin, which was responsible for high DC maturation and cellular uptake. After three doses of biomimetic nanotoxoid vaccination, the mice received the lethal bolus toxin. Biomimetic nanotoxoid vaccinated mice showed a 75% survival rate, compared to the 20% survival rate of non-vaccinated mice [141] . A biomimetic nanosponge was reported ( Figure 8 ) by using PLGA NPs as a core, and RBC membrane as a surface coating. The RBC membrane acts as a substrate for PFTs, which can induce an alpha-toxin onto the surface, reduce hemolytic activity, and enhance the blood circulation time [142] .