Antigen-Containing Silk Nanoparticles: A New Potential as Oral Vaccine Carriers

Purpose: Oral vaccines are safer, easier to administer, and more cost-effective than injectable vaccines are. They induce systemic and mucosal immunity, thereby providing broad protection. However, developing an orally administered vaccine that can traverse the stomach and safely reach the intestinal tract to induce antigen-specific immune responses is challenging. Recently, many effective nanoparticle (NP) drug delivery systems have been developed. Various polymeric materials, including synthetic biodegradable and natural polymers, have been used as drug delivery matrices. Silk fibroin, a natural polymer, shows promise as a suitable material for drug delivery due to its biocompatibility, biodegradability, and aqueous processability. In this study, to investigate the potential of silk proteins as oral vaccine carriers, we prepared ovalbumin (OVA)-containing silk NPs through salting-out an aqueous solution of degummed fibers and non-degummed cocoons obtained from silkworms ( Bombyx mori ) and examined whether oral administration could induce OVA-specific antibody production in mice. Methods: For the OVA-containing silk NPs, OVA was prepared through salting-out a mixture of OVA and an aqueous solution of cocoons or degummed fibers. OVA-specific antibody production in mice orally administrated OVA-containing silk NPs was analyzed using ELISA. Silk NP delivery to the intestinal tract of mice was monitoring using FITC-incorporated silk. The FITC-labeled cocoon and degummed fiber NPs were incubated with peritoneal macrophages, and their internalization observed using fluorescence imaging. Results: OVA-containing silk NPs can be delivered to the intestinal tract after oral administration to mice and subsequently induce OVA-specific serum IgG and intestinal IgA production without the need for adjuvants. Moreover, internalization of FITC-labeled cocoon or degummed fiber NPs into peritoneal macrophages was observed in vitro. Conclusion: Overall, silk NPs are promising oral vaccine carriers that can deliver antigens to the intestinal tract while avoiding decomposition by gastric acid and digestive enzymes, thereby facilitating the activation of mucosal and systemic immunity. Keywords: fibroins, nanoparticles-based drug delivery system, oral administration, antibody production