Most vaccines currently available are designed for parenteral administration, typically delivered through injections directly into the body. While this method is effective, it often causes discomfort, pain, and fear, which can negatively impact vaccination rates. Additionally, intramuscular administration may not always generate an optimal immune response against pathogens that primarily invade the body via mucosal surfaces.
Vaccines designed for mucosal delivery are available in innovative systems that offer simple, painless administration, potentially improving patient acceptance and compliance. Among these, mucoadhesive films (MAF) represent one of the patient-friendly delivery method. Mucoadhesive films are applied to the buccal mucosa, which is well-vascularized, and partially permeable, allowing for efficient delivery of active substances. Due to its accessibility and abundance of immune cells, which are key to triggering the innate and acquired immune response, the buccal mucosa has great potential for vaccination.
In this doctoral dissertation, we developed bilayer films comprising a mucoadhesive layer containing the vaccine, which adheres to the buccal mucosa, and an impermeable protective layer to prevent undesired dissolution of the vaccine in the oral cavity. To prepare the films, we tested various combinations of natural and synthetic polymers, sugars, and appropriate solvents. Among the tested formulations, a mixture of trehalose, pullulan, and sucrose proved to be the most suitable. We investigated the applicability of these films for delivering various vaccine platforms, including plasmids, viral vectors, and lipid nanoparticles containing mRNA (mRNA/LNP). The successful delivery of this platform was first tested on reporter molecules, followed by immunization of laboratory animals with films containing an mRNA/LNP vaccine against SARS-CoV-2. In the group that received MAF as a booster dose following initial intramuscular immunization, the production of IgG antibodies was comparable to standard intramuscular vaccination. Additionally, groups that received the mucosal vaccine in the form of MAF showed elevated levels of IgA antibodies, which play a critical role in neutralizing pathogens at mucosal surfaces. These findings demonstrate that combining systemic and mucosal administration induces a stronger and more comprehensive immune response, underscoring the potential advantages of combined vaccination strategies. The study highlights the benefits of MAFs as booster doses, particularly for protection against respiratory infections.
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