The development of mucosal vaccinations for oral transmucosal delivery using nanofabrication processes

• Κύριος συγγραφέας: Mohamed Burhan Awad, Ayah
• Άλλοι συγγραφείς: Αντιμησιάρη, Σοφία
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Antimicrobial resistance; Subunit protein vaccines; Polymeric patches; Mucosal immunization; Μικροβιακή αντοχή; Εμβόλια υπομονάδας πρωτεΐνης; Πολυμερή έμπλαστρα; Βλεννογονική ανοσοποίηση

It is estimated that by 2050, globally 10 million people will die due to antimicrobial resistance (AMR) related illness. Therefore, taking the world back to the pre-antibiotic era, where millions of people died from infectious diseases. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. It is well documented that the local triggering of mucosal immunity is an effective first line protection against pathogens invasion. In addition, it can induce cell-mediated immunity and is therefore capable of stimulating both arms of the immune system. Another interesting advantage of mucosal immunization is its ability to induce immune protection both systemically as well as at distal mucosal sites. Therefore, using the non-invasive sublingual mucosal route for vaccination can be exploited a to induce protective immunity, while maintaning maximal patient compliance. The pathogen derived subunit protein vaccines, in addition to the feasibility of their economic and large scale production, they possess many merits in vaccination making them the most popular antigens for vaccine design. A major challenge faced with subunit protein vaccine development is their potential to degrade and become inactive during the formulation development process. Due to their weak immunogenic response, subunit protein vaccines usually require coadministration of vaccination adjuvants. In our study, we investigated the use of electrohydrodynamic atomization to produce polymeric nanofibrous sublingual patches for the oral transmucosal delivery of biologics as an essential step towards the development of mucosal vaccinations. In our study, the encapsulation and protective potential of the amphiphilic polymer Soluplus (BASF) and sulfobutylether-β-cyclodextrin (Cylclolab) was explored against the effect of increasing electrospinning voltage. A model protein lysozyme was used due to its similarity to pneumococcal surface protein A, and changes to protein structure and biological activity on formulation was investigated. This project was support by BASF and Cyclolab who kindly donated Soluplus and sulfobutylether-β-cyclodextrin respectively.