Bimodal Targeting of Human Leukocytes by Fc- and CpG-Decorated Polymersomes to Tune Immune Induction

The use of well-defined nanovesicles composed of amphiphilic block copolymers (polymersomes) for delivery of adjuvants and antigens is a promising strategy for vaccine development. However, the potency of nanoparticle vaccines depends on efficient interaction with and activation of cells involved in antigen presentation, which can be achieved by targeting cellular receptors. Here, we showed that the Fc fragment display on the polymersome surface resulted in markedly improved interactions with granulocytes, monocytes, and NK cells, while for naked polymersomes, virtually no binding to leukocytes was observed. Moreover, CpG-decorated polymersomes were found to also interact with T and/or B cells. Interestingly, whole blood stimulations with Fc fragment and CpG-decorated polymersomes induced interleukin (IL)-6, IL-8, and TNF-alpha production, while naked polymersomes did not induce any cytokine production. In conclusion, specific immune induction by polymersomes can be controlled using bimodal targeting of different immune receptors, which is an essential feature for targeted vaccine delivery.

Automated summary

The study demonstrated that displaying Fc fragments on the surface of polymersomes significantly increased interactions with granulocytes, monocytes, and NK cells, while CpG-decorated polymersomes were found to also interact with T and/or B cells. Stimulation of whole blood with Fc fragments and CpG-decorated polymersomes induced the production of interleukin, while naked polymersomes did not induce cytokine production. This suggests that bimodal targeting of different immune receptors on polymersomes can control specific immune induction for targeted vaccine delivery.